引用第7楼immunol于2006-09-21 10:32发表的“”:merck很强啊，呵呵，对这里还是比较了解的。现在复旦招的本科生都要进入复旦学院学习一年，以后会延长，直至达到不分专业，可以说是复旦大学的根本；主要是通过通识教育和一系列核心课程，打上"复旦"烙印，培养创新型人才。应该承认上医基础医学院最近是有些没落了，上二医的免疫整体要强于上医；不过上医的免疫只有熊老师一个人顶着，社会职务又如此之多，呵呵。上医还是有些人申请的经费甚至以“亿”为单位，不知道是不是很多，我感觉还是不少，呵呵。“不仅仅是免疫，上医的药理，细胞生物，解剖，遗传，病生，寄生虫，甚至生化，病理等教研室也都差不太多”，这个我有些不敢苟同，上医免疫系每年的SCI文章数量占医学院1/5~1/4，SCI总分数占1/4~1/3，应该讲，各个实验室之间的差距还是有的。.......
占的比例高只是说明别的地方少了，并不能说自己多的。如果上医免疫拿到sibs或者二医，那么比例不会有这么高了，总分数应该更低。
上面所讲的经费是纵向的，现在纵向最大的就是973，如果算横向的话，那根本就没法比较了。上海医工院可能大家知道的不是太多，除了药学专业。那是一个主要研究仿制药物的研究所，文章没有什么CNS，牛人也只有一位院士，但是大多数老板的经费应该远胜上医，北医甚至中科院的很多老板。
问题是，横向还是纵向更能反映水平呢？
复旦学院这样的非专业性学院，熊院长去管理和管理学院的老师去管理有什么特别的不同么？ 不知道管理这样的学院会不会花费很多时间。
最近2年文章还是不错的。
1: J Leukoc Biol. 2006 Sep 15; [Epub ahead of print]
Targeted in vivo expression of IFN-{gamma}-inducible protein 10 induces specific
antitumor activity.
Yang X, Chu Y, Wang Y, Zhang R, Xiong S.
*Department of Immunology of Shanghai Medical College and Institute for
Immunobiology, Fudan University, Shanghai, People's Republic of China; and
Immunology Division, E-Institutes of Shanghai Universities, Shanghai, People's
Republic of China.
Although it is known that the chemoattractant effect of IFN-gamma inducible
protein 10 (IP-10), a CXC chemokine (CXCL10), plays an important role in T
cell-mediated antitumor immunity in vivo, whether IP-10 is involved in
modulating the proliferation, survival and functional activation of
tumor-specific T cells remains poorly investigated. Using an experimental mouse
tumor model, we demonstrated that the in vivo growth of 4T1 tumor cells
harboring IP-10 gene (4T1-IP-10) was inhibited. Mice inoculated with 4T1-IP-10
tumor cells expressing functional IP-10 survived over 90 days, whereas mice
injected with control parental 4T1 cells and mice of control 4T1 cells
transduced with control plasmid all succumbed to the tumor by day 38 after tumor
inoculation. Mechanical analysis showed that targeted expression of IP-10 in 4T1
tumor cells markedly enhanced the infiltration of tumor-specific T cells into
the 4T1-IP-10 tumor. These tumor infiltrating T lymphocytes (TILs) recruited by
IP-10 were potent cytolytic killers against 4T1 tumor cells and were able to
proliferate and produce high levels of IFN-gamma in response to 4T1 cells. In
vivo administration of IP-10-recruited TILs induced vigorous proliferation of
these TILs in situ in the 4T1-IP-10 tumor but not in the 4T1-pcDNA3 and parental
4T1 tumors. Furthermore, culture of TILs together with recombinant IP-10
significantly enhanced the proliferation and expansion of IP-10-recruited TILs
in response to 4T1 tumor antigens. These results suggest that IP-10 is not only
able to chemoattract tumor-specific T cells into the local tissue, but also
enhance the proliferation, survival, and functional activation of these TILs,
leading to the tumor regression. Thus, targeted expression of IP-10 in vivo will
allow for the development of a novel approach for immunotherapy of tumor.
PMID: 16980511 [PubMed - as supplied by publisher]
2: Vaccine. 2006 Apr 5;24(15):2966-74. Epub 2005 Dec 20.
Vaccination with IFN-inducible T cell alpha chemoattractant (ITAC) gene-modified
tumor cell attenuates disseminated metastases of circulating tumor cells.
Yang X, Chu Y, Wang Y, Guo Q, Xiong S.
Department of Immunology and Center for Gene Immunization and Vaccine Research,
Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai
200032, PR China.
Immunotherapeutic strategies for metastatic diseases are being developed.
IFN-inducible T cell alpha chemoattractant (ITAC) has been demonstrated to be
able to induce Th1-type immune response. However, the effects of ITAC on the
tumor metastasis have not been fully understood. In the present study, the
ITAC-modified tumor cell vaccine in inhibiting the disseminated pulmonary
metastasis was evaluated. ITAC-modified tumor cell vaccine 4T1-ITAC was
developed by stably transfecting 4T1 cells with pcDNA3-ITAC plasmid. Mice were
vaccinated with 4T1-ITAC. Mice vaccinated with 4T1-pcDNA3 and 4T1 were used as
controls. Specific cellular immune responses against 4T1 were tested by in vitro
proliferation, cytokine production and cytotoxic assay. The number of clonogenic
metastatic tumor cells and metastatic forci on the surface of lung were counted
by histological examination. Results showed that a significant enhancement of
proliferative and cytotoxic activities accompanied with increased IFN-gamma and
TNF-alpha production as well as decreased IL-4 production were obtained from the
mice vaccinated with 4T1-ITAC. The number of clonogenic metastatic tumor cells
in the mice vaccinated with 4T1-ITAC cells reduced markedly and no visible
metastasis was found in the lungs of the 4T1-ITAC vaccinated mice. Consequently,
the survival rate was dramatically increased in these mice. Taken together, our
results demonstrated that ITAC-modified tumor cell vaccine can enhance the
anti-tumor immunity and reduce the incidence of disseminated metastasis.
PMID: 16503368 [PubMed - in process]
3: FASEB J. 2006 Jan;20(1):50-8.
Agrin is involved in lymphocytes activation that is mediated by
alpha-dystroglycan.
Zhang J, Wang Y, Chu Y, Su L, Gong Y, Zhang R, Xiong S.
Department of Immunology, Shanghai Medical College of Fudan University, 138
Yixueyuan Road, Shanghai, 200032, China.
It is well established that agrin, an extracellular matrix protein, plays a
crucial role in the formation of neuromuscular junctions. Recent evidence
indicates that agrin also contributes to immunological synapse formation.
However, little is known about how agrin induces the activation of lymphocytes
and whose receptors mediate its regulatory effects on these cells. In the
present study, agrin was detected in lymphocytes. Up-regulation of agrin
expression was involved in lymphocyte activation whereas down-regulation of its
expression led to inhibition of both antigen-specific and nonspecific lymphocyte
activation, indicating an intrinsic role for agrin in the activation of
lymphocytes. Unexpectedly, unlike that found in muscle cells where there is
coexpression of muscle-specific kinase (MuSK) and alpha-dystroglycan receptors
for agrin, only alpha-dystroglycan could be detected in lymphocytes. Confocal
examination showed that alpha-dystroglycan colocalized with agrin in forming the
immunological synapse. Down-regulation of alpha-dystroglycan expression
inhibited lymphocyte activation even in the presence of agrin. However, agrin
involved in down-regulation of alpha-dystroglycan receptors did not increase the
inhibitory effect on lymphocytes activation. The anti-alpha-dystroglycan
antibody also induced lymphocytes activation. Taken together, these findings
strongly indicate that agrin and alpha-dystroglycan mediate lymphocyte
activation. Furthermore, agrin-involved lymphocyte activation is mediated by
alpha-dystroglycan.
PMID: 16394267 [PubMed - indexed for MEDLINE]
4: Cancer Gene Ther. 2006 May;13(5):510-9.
Th2-dominated antitumor immunity induced by DNA immunization with the genes
coding for a basal core peptide PDTRP and GM-CSF.
Chu Y, Xia M, Lin Y, Li A, Wang Y, Liu R, Xiong S.
Department of Immunology, Key Laboratory of Molecular Medicine of Ministry of
Education, Shanghai Medical College of Fudan University, Shanghai, China.
Our previous study showed that DNA vaccination with a plasmid vector encoding a
core peptide of mucin1 (PDTRP) provided modest protection against challenge with
tumor cells that expressed mucin1 protein. We report here that a DNA vaccine
comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus
induced better protection against tumor challenge. The increased protection was
directly correlated with a stronger PDTRP-specific immune response induced by
the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP
antigen induced a greater PDTRP-specific Th proliferation, antibodies, and
cytotoxicity. Interestingly, the modified plasmid vaccine predominantly enhanced
the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody
ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and
IFN-gamma mRNA in spleen cells from vaccinated mice. In addition, protection
against tumor challenge in vaccinated mice showed that there was no significant
change in mice survival after in vivo CD8+CTL depletion, indicating that
antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene
vaccine was dominated by Th2 immune response.
PMID: 16341143 [PubMed - indexed for MEDLINE]
5: Clin Cancer Res. 2005 Dec 1;11(23):8273-80.
Differential expression of CXCR4 is associated with the metastatic potential of
human non-small cell lung cancer cells.
Su L, Zhang J, Xu H, Wang Y, Chu Y, Liu R, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine, Ministry of
Education, Shanghai Medical College, Fudan University, Shanghai, People's
Republic of China.
PURPOSE: To evaluate the relation between CXCR4 expression and the presence of
metastatic disease in human non-small cell lung cancer (NSCLC) patients and
investigate whether modulation of CXCR4 expression could serve as a potential
pathway in preventing metastasis of NSCLC. EXPERIMENTAL DESIGN: CXCR4 expression
in 36 patients with NSCLC and 10 normal lung tissues was detected by real-time
PCR and immunohistochemistry. CXCR4 expression in two human NSCLC clones (95C
and 95D) with different metastatic potential was determined by real-time PCR and
flow cytometry. 95C and 95D cells were transfected with the plasmid DNA
containing CXCR4 coding gene or CXCR4 antisense nucleotide fragment,
respectively, and the effects on in vitro cell migration, invasion, and adhesion
and in vivo metastasis were measured. RESULTS: Up-regulated expression of CXCR4
was detected in 34 tumors, which were further divided into 17 high expression
cancers and 17 low expression cancers by their staining intensities. High CXCR4
tumors (13 of 17) were more prone to clinical metastasis in comparison with low
expression tumors. CXCR4 was differentially expressed in 95C and 95D cells with
low or high metastatic potential, and the surface expression of CXCR4 were 50%
up-regulated or down-regulated following the stable transfection. The metastatic
potential of NSCLC in vitro, such as migration, invasion, and adhesion, were
significantly enhanced or impaired. In addition, neutralizing the interactions
of stromal cell-derived factor-1/CXCR4 in vitro with CXCR4-specific antibodies
inhibited the CXCR4-dependent migration, invasion, and adhesion. Furthermore,
s.c. inoculation of lung cancer cells with low expression of CXCR4 in nude mice
showed 0- to 2-fold decrease in lung metastatic foci than that with high
expression of CXCR4. CONCLUSIONS: Differential expression of CXCR4 is associated
with the metastatic potential of human NSCLC, raising the possibility that
blockade of CXCR4/stromal cell-derived factor-1 interaction may lead the way to
design novel therapeutic tools for the treatment of metastatic NSCLC patients.
PMID: 16322285 [PubMed - indexed for MEDLINE]
6: Vaccine. 2005 Oct 25;23(44):5160-7.
All-trans retinoic acid biases immune response induced by DNA vaccine in a Th2
direction.
Yu S, Xia M, Xu W, Chu Y, Wang Y, Xiong S.
Department of Immunology, Shanghai Medical College, Fudan University, Shanghai,
200032, P.R. China.
Vitamin A deficiency diminishes Th2-mediated Ab responses. Providing Vitamin A
or its active metabolites reverses this defect. All-trans retinoic acid (ATRA),
an acid derivation of Vitamin A, regulates the balance of immune response
induced by TR421-hCGbeta DNA vaccine. Compared to DNA vaccine alone or treatment
with vehicle, significantly higher level of antibody against the protein encoded
by DNA vaccine was observed in mice 6 weeks after the first immunization. The
IgG2a/IgG1 ratio was lower in mice treated with ATRA. We also found that
treatment with ATRA also diminishes specific cellular immune response induced by
gene immunization by measuring the marker of cellular immune response. We
conclude that ATRA biases the immune response to Th2 direction induced by DNA
vaccine and acts as a candidate adjuvant and immunomodulatory molecule.
PMID: 16040168 [PubMed - indexed for MEDLINE]
7: Immunol Lett. 2005 Jul 15;99(2):186-92. Epub 2005 Mar 25.
Single B or T-cell epitope-based DNA vaccine using modified vector induces
specific immune response against hepadnavirus.
Xu HB, Xu W, Chu YW, Wang Y, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine of the
Ministry of Education, Shanghai Medical college of Fudan University, P.R. China.
Epitope-based DNA vaccine is an effective and powerful approach against a
variety of pathogens or tumors. In present study, we reconstructed a vector that
could effectively express short B and T-cell epitope of duck/hepatitis B virus,
and investigated the role of the epitope-based DNA vaccination. The pUC19 was
modified by inserting the compact transient framework (CTF), including HCMV IE1
promoter, enhancer, Kozak sequence, dual stop codon and 3' terminal bovine
growth hormone terminal signal and so on. This modified vector was designated
pEC(K) and supposed to effectively express short peptide. A well-defined single
B-cell and T-cell epitope encoding gene of duck/hepatitis B virus has been
synthesized as candidate epitope and cloned into pEC(K) plasmid, respectively.
Transfection of the recombinant DNA into C(2)C(12) cell showed that modified
plasmid could effectively express both the single B-cell and T-cell short
epitope in the culture supernatant as confirmed by dot immunoblot assay (DIA).
The recombinant single B and T-cell epitope-based DNA vaccine was administrated
to C57BL/6 mice and could greatly induce specific humoral and CTL response. In
addition, the specific antibody against B epitope could specifically bind to the
DHBV particles. This report demonstrated that single epitope-based DNA vaccine
using modified plasmid vector pEC(K) could induce effective specific immune
responses and could be of great use for DNA vaccines.
PMID: 16009269 [PubMed - indexed for MEDLINE]
8: Infect Immun. 2005 Jul;73(7):4007-16.
Involvement of up-regulated CXC chemokine ligand 16/scavenger receptor that
binds phosphatidylserine and oxidized lipoprotein in endotoxin-induced lethal
liver injury via regulation of T-cell recruitment and adhesion.
Xu H, Xu W, Chu Y, Gong Y, Jiang Z, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of
Education, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road,
Shanghai 200032, People's Republic of China.
A murine model of endotoxin-induced lethal liver injury induced by Mycobacterium
bovis BCG plus lipopolysaccharide (LPS) has been widely accepted and used. It
has been reported that T cells play an important role in the pathogenesis of
liver damage in this model. However, the precise mechanisms involved in
regulation of the trafficking of effector T cells need to be elucidated. In the
present study, we first reported that CXCL16/SR-PSOX (CXC chemokine ligand
16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein), a
chemokine containing both membrane-anchored and soluble forms, was strongly
up-regulated and predominantly distributed in the vascular endothelium in the
injured liver tissue in the model. The secretory and membrane-anchored
CXCL16/SR-PSOX functioned as a chemokine and an adhesive molecule, respectively,
to attract T cells to a tumor necrosis factor alpha-activated endothelial cell
line (SVEC) in vitro. To further identify the pathophysiological roles of
CXCL16/SR-PSOX in the liver injury, the anti-CXCL16 antibody was administered to
the BCG-primed mice before LPS challenge in vivo. Significant protection effects
were observed with 70% of mice regarding lethality, the massive necrosis in the
liver was reduced, and the intrahepatic infiltrating T cells were significantly
inhibited. Taken together, these findings strongly suggest that functional
CXCL16/SR-PSOX, as both a chemokine and an adhesion molecule, may be involved in
the pathogenesis of the endotoxin-induced lethal liver injury via recruitment
and adhesion of activated T cells to the vascular endothelium.
PMID: 15972488 [PubMed - indexed for MEDLINE]
9: Immunol Lett. 2005 Jul 15;99(2):217-27. Epub 2005 Apr 25.
Origin and anti-tumor effects of anti-dsDNA autoantibodies in cancer patients
and tumor-bearing mice.
Lv S, Zhang J, Wu J, Zheng X, Chu Y, Xiong S.
Department of Immunology, Shanghai Medical College of Fudan University, PR
China.
In the present investigation, we detected anti-dsDNA autoantibodies in cancer
patients and modeled the production of anti-dsDNA autoantibodies by inoculating
tumors in BALB/c mice. Moreover, induction of anti-dsDNA autoantibodies by
immunization with inactivated tumor cells and their DNA indicated that DNA of
tumor cells was probably the primary antigen, which was supported by the
significantly increasing levels of sera free DNA in cancer patients and
tumor-bearing mice. cELISA and indirect immunofluorescence assay showed that the
anti-dsDNA autoantibodies could bind to the surface components of tumor cells.
In vitro assay showed that immunosera at week 6 from immunized mice displayed
significant cytotoxicity to tumor cells compared to that of negative control,
but no cytotoxicity mediated by immunosera at week 22 was observed. In addition,
by flow cytometry and electrophoresis of fragmented DNA, the cytotoxicity might
probably be mediated by apoptosis. Our data also showed that the ability of the
anti-dsDNA autoantibodies to induce apoptosis of SP2/0 and Wehi 164 cells was
significantly correlated (r = 0.990, p < 0.01 and r = 0.901, p < 0.05) with
their functional affinity. In vivo, the growth of solid tumors was significantly
inhibited in the immunized mice inoculated directly with SP2/0 and Wehi 164
cells, or in the naive mice which were inoculated with SP2/0 cells preincubated
with immunosera containing anti-dsDNA autoantibodies. In conclusion, we
demonstrated the origin of anti-dsDNA autoantibodies in cancer patients and
tumor-bearing mice. And our data also showed that these autoantibodies revealed
anti-tumor effect by inducing apoptosis.
PMID: 15869804 [PubMed - indexed for MEDLINE]
10: Rheumatology (Oxford). 2005 Sep;44(9):1108-14. Epub 2005 Apr 19.
Comment in:
Rheumatology (Oxford). 2005 Sep;44(9):1086-9.
Induction of systemic lupus erythematosus-like syndrome in syngeneic mice by
immunization with activated lymphocyte-derived DNA.
Qiao B, Wu J, Chu YW, Wang Y, Wang DP, Wu HS, Xiong SD.
Department of Immunology, Shanghai Medical College of Fudan University, P.R.
China.
OBJECTIVES: Systemic lupus erythematosus (SLE) is the prototype of autoimmune
disease and the mechanisms underlying the disease have not yet been elucidated.
Thus, animal models of SLE would facilitate investigation of pathogenetic
mechanisms involved in the development of the disease. This study characterizes
a murine model of SLE-like syndrome induced by syngeneic activated
lymphocyte-derived DNA (referred to as ALD DNA). METHODS: Normal BALB/c mice
were immunized subcutaneously with highly purified ALD DNA. Anti-double-stranded
DNA (anti-dsDNA) antibodies were determined by enzyme-linked immunosorbent
assay. Other SLE-associated autoantibodies were examined by indirect
immunofluorescence and anti-ENA (extractable nuclear antigen) profile assay.
Pathological changes were analysed by light microscopy and electron microscopy.
Kidney cryostat sections were viewed by immunofluorescence for the presence of
glomerular IgG and C3 deposits. Proteinuria was measured by Coomassie brilliant
blue assay. RESULTS: High levels of anti-dsDNA antibodies and other
autoantibodies frequently appearing in SLE were detectable in the sera of ALD
DNA-immunized mice. Glomerulonephritis and glomerular deposition of IgG plus C3
were observed in the kidney sections. Moreover, proteinuria was seen in the
immunized mice. CONCLUSIONS: SLE-like syndrome can be induced by ALD DNA in
normal mice. This induced model may be useful for elucidating the mechanisms
involved in autoimmunity to DNA and the development of SLE.
PMID: 15840592 [PubMed - indexed for MEDLINE]
11: Virology. 2005 Apr 10;334(2):255-63.
Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T
lymphocytes induced by a CTL epitope-based DNA vaccine.
Xu W, Chu Y, Zhang R, Xu H, Wang Y, Xiong S.
Department of Immunology, Shanghai Medical College of Fudan University,
Shanghai, PR China.
CD8(+) T cells play a critical role in protective immunity against Hepatitis B
Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can
be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL)
responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc(18-27),
was constructed. Intramuscular immunization of C57BL/6 mice with this DNA
vaccine resulted in successful induction of HBV-specific CTL responses. In order
to promote transportation of the peptide into endoplasmic reticulum (ER) to bind
to MHC class I molecules for optimal class I antigen presentation, an ER
targeting sequence (ERTS) was fused with the C(18-27) encoding gene. ERTS fusion
significantly enhanced specific CD8(+) T cell responses in terms of CTL
cytolysis as well as IFN-gamma secretion. This enhancement was correlated with
promoted epitope presentation on target cell surface. We report here an enhanced
immunogenicity of an epitope-based DNA vaccine using an ER targeting signal
sequence, which has significant implications for future design of therapeutic
HBV vaccine.
PMID: 15780875 [PubMed - indexed for MEDLINE]
12: DNA Cell Biol. 2004 Dec;23(12):807-14.
Application of a gene vaccine targeting HER-2/neu in immunocontraception.
Ni J, Ni Y, Wang X, Xu W, Wang Y, Xiong S.
Department of Immunology, Shanghai Medical College of Fudan University,
Shanghai, People's Republic of China.
HER-2/neu was widely used as a target for tumor prevention and therapy because
of its overexpression in many tumors. However, it also plays an important role
in proliferation of endometrium, embryo implantation, and development. Here,
HER-2/neu was used in immunocontraception. A gene vaccine encoding the
extracellular domain of human HER-2/neu was constructed. After immunization, it
especially elicited both humoral and cellular responses in mice. Embryo
implantation was interfered by intravenous and intraluminal injection of
anti-HER-2/neu serum or lymphocytes. Lower fertility was induced after
vaccination when compared with the control groups, while injuries to the uterus
and ovary were not observed. Our results suggested a new and impactful target
for contraceptive vaccines development.
PMID: 15684707 [PubMed - indexed for MEDLINE]
13: Transpl Immunol. 2004 Dec;13(4):283-8.
The CD28 peptidemimic can induce mixed chimerism and prolong the survival of
cardiac allografts.
Chen J, He Q, Xu H, Su L, Zhang J, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine of the
Ministry of Education, Fudan University, Shanghai 200032, PR China.
Costimulatory blockade with CD28 peptidemimic (CD28PM, CD28 PM was synthesized
by solid phase synthetic methods) prolongs cardiac allograft survival in mice,
but has not reliably induced tolerance when used alone. In the current studies,
we evaluated the effect of adding B7 blockade to a chimerism inducing
nonmyeloablative regimen in mice and observed a significant improvement of donor
bone marrow cells (BMC) engraftment, which had been associated with mixed
chimerism and long-term survival of cardiac allografts. The mixed lymphocyte
reaction (MLR) and the ear pinna cardiac transplantation model were performed to
evaluate the effects of CD28PM in induction of specific immune hypo-response and
extension of allograft survival. The expressed rates of B7.1 and B7.2 on the
C57BL/6 splenocytes were 56.25% and 20.52%, respectively. The specific
hypo-response status was established after immunization with CD28PM pre-treated
donor splenocytes and the average inhibition rate was only 43% compared with
normal control. Subsequently, a total number of 2 x 10(7) bone marrow cells per
mouse were implanted to the recipients. The allogenic chimerism was obviously
observed with the rate as high as 8.84% (mean) at the time point of day 14.
During the first 50 days post bone marrow transfusion (BMT) the chimerism rate
declined stepwise. But from 50 to 100 days, the chimerism rate sustained in a
range of 3.35% to 4.6%. The results of transplantation experiments showed the
survival of allgenic cardiac grafts were maintained over 100 days in recipients.
Thus, donor BMC engraftment with mixed chimerism appears essential for induction
of allograft tolerance using this conditioning regimen. Mixed chimerism
approach, by the addition of CD28-B7 costimulatory blockade with CD28PM, has
been shown to establish mixed chimerism and induce cardiac allograft tolerance
in mice.
PMID: 15589741 [PubMed - indexed for MEDLINE]
14: J Virol. 2004 Nov;78(22):12548-56.
Coxsackievirus group B type 3 infection upregulates expression of monocyte
chemoattractant protein 1 in cardiac myocytes, which leads to enhanced migration
of mononuclear cells in viral myocarditis.
Shen Y, Xu W, Chu YW, Wang Y, Liu QS, Xiong SD.
Department of Immunology, Shanghai Medical College of Fudan University, 138
YiXueYuan Rd., Shanghai 200032, People's Republic of China.
Coxsackievirus group B type 3 (CVB3) is an important cause of viral myocarditis.
The infiltration of mononuclear cells into the myocardial tissue is one of the
key events in viral myocarditis. Immediately after CVB3 infects the heart, the
expression of chemokine(s) by infected myocardial cells may be the first trigger
for inflammatory infiltration and immune response. However, it is unknown
whether CVB3 can induce the chemokine expression in cardiac myocytes. Monocyte
chemoattractant protein 1 (MCP-1) is a potent chemokine that stimulates the
migration of mononuclear cells. The objective of the present study was to
investigate the effect of CVB3 infection on MCP-1 expression in murine cardiac
myocytes and the role of MCP-1 in migration of mononuclear cells in viral
myocarditis. Our results showed that the expression of MCP-1 was significantly
increased in cardiac myocytes after wild-type CVB3 infection in a time- and
dose-dependent manner, which resulted in enhanced migration of mononuclear cells
in mice with viral myocarditis. The migration of mononuclear cells was partially
abolished by antibodies specific for MCP-1 in vivo and in vitro. Administration
of anti-MCP-1 antibody prevented infiltration of mononuclear cells bearing the
MCP-1 receptor CCR2 in mice with viral myocarditis. Infection by UV-irradiated
CVB3 induced rapid and transient expression of MCP-1 in cardiac myocytes. In
conclusion, our results indicate that CVB3 infection stimulates the expression
of MCP-1 in myocardial cells, which subsequently leads to migration of
mononuclear cells in viral myocarditis.
PMID: 15507642 [PubMed - indexed for MEDLINE]
15: Clin Exp Immunol. 2004 Nov;138(2):245-50.
Allogenic donor splenocytes pretreated with antisense peptide against B7 prolong
cardiac allograft survival.
Chen J, He Q, Zhang R, Chu Y, Wang Y, Liu Q, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of
Education, Fudan University, Shanghai, China.
The interaction of T cell CD28/CTLA-4 receptors with B7 on antigen-presenting
cells (APCs) represents an important co-stimulatory pathway in T cell activation
or anergy. Our previous study indicated that recipients immunized with allogenic
donor immature dendritic cells (DCs) or resting B cells could induce specific
immune tolerance and prolong allograft survival. A possible mechanism for this
observation is that the expression of B7 molecules is either at a low level or
lacking on these cells. The present study investigates whether blockade of B7
molecules on donor splenocytes with a B7 antisense peptide (B7AP), i.e. a
peptide analogue of the CD28-binding region, could induce specific immune
tolerance and prolong allograft survival in the recipients. Both the lymphocyte
proliferation reaction and the mice pinna cardiac allograft experiment were
performed to evaluate the role of B7AP in inducing specific immune tolerance in
recipients in vitro and in vivo. The results showed that 56.65% and 20.52% of
C57BL/6 splenocytes expressed B7.1 and B7.2 molecules, respectively, on their
cell surface. There were no significant changes of the B7 expression on such
splenocytes after being treated by the B7AP (53.28% and 19.06%, respectively).
B7AP inhibited the mixed lymphocyte reaction by up to 38.4% and a dose-response
correlation was observed for inhibition. The recipients (BALB/c) immunized with
B7AP-pretreated C57BL/6 splenocytes induced a specific immune hypo-response
(43%versus control) and notably prolonged survival of the C57BL/6 cardiac
allograft by up to 20.3 days. In contrast to the normal saline group (average:
8.6 days) and FTD(10) control peptide group (<4 days), the cardiac allograft
survival of the test group was extended for an additional 11.7 days. These
results strongly support the notion that immunization with donor splenocytes,
which had been pretreated with B7AP, induced specific immune tolerance and
prolonged allograft survival in the recipients.
PMID: 15498033 [PubMed - indexed for MEDLINE]
16: Vaccine. 2004 Sep 9;22(27-28):3603-12.
Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3
protection.
Xu W, Shen Y, Jiang Z, Wang Y, Chu Y, Xiong S.
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of
Education, Shanghai Medical College, Fudan University, Shanghai 200032, PR
China.
Coxsackievirus B3 infections are common causes of acute and chronic myocarditis
with no effective prophylactic treatment available. We describe here a
prophylactic strategy using chitosan-DNA intranasal immunization to induce CVB3
specific immune responses. Intranasal administration with chitosan-DNA complex
prepared by votexing DNA with chitosan, a natural mucus absorption enhancer,
resulted in transgenic DNA expression in mouse nasopharynx. Mice immunized with
chitosan-DNA (pcDNA3-VP1) encoding VP1, major structural protein of CVB3,
produced much higher levels of serum IgG and mucosal secretory IgA compared to
mice treated with pcDNA3-VP1 or pcDNA3. Increased virus-specific cytotoxic
activity of spleen cells derived from chitosan-DNA vaccinated mice was also
determined. Chitosan-pcDNA3-VP1 intranasal immunization resulted in 42.9%
protection of mice against lethal CVB3 challenge and a significant reduction of
viral load after acute CVB3 infection. Meanwhile no myonecrosis or infiltrating
immune cells indicating ongoing myocarditis was detected in hearts of surviving
mice treated with chitosan-DNA. Together, Our data show that intranasal delivery
of chitosan-DNA vaccine successfully induced mucosal SIgA secretion and might be
a promising vaccine candidate to protect against CVB3 infection.
PMID: 15315839 [PubMed - indexed for MEDLINE]
