Severe Depletion of CD4+CD25+ Regulatory T Cells from the Intestinal Lamina Propria but not Peripheral Blood or Lymph Nodes During Acute SIV Infection
Amanda J. Chase, Ahmad R. Sedaghat, Jennifer R. German, Lucio Gama, M. Christine Zink, Janice E. Clements, and Robert F. Siliciano*
Departments of Medicine and Comparative Medicine, Johns Hopkins University School of Medicine, and Howard Hughes Medical Institute, Baltimore, Maryland
* To whom correspondence should be addressed. Email:
rsiliciano@jhmi.edu.
Abstract
CD4+CD25+ regulatory T cells (Tregs) suppress the activation and proliferation of effector lymphocytes. In HIV-1 infection Tregs play a significant role in controlling the apoptotic loss of uninfected CD4+ T cells resulting from high levels of generalized immune activation. During acute HIV-1 infection more than 50% of CD4+ T cells are depleted from the gastrointestinal lamina propria. To elucidate the role of Tregs in HIV-1-induced depletion of CD4+ T cells in the gut-associated lymphoid tissue (GALT), we first determine the distribution of Tregs in a setting of acute infection using the SIV/pigtailed macaque model of HIV-1 disease. CD4+ T cells from the GALT, lymph nodes, and peripheral blood were isolated on days 4, 14, and 114 post-inoculation from SIV-infected pigtailed macaques. Quantitative real-time RT-PCR was used to quantitate FOXP3 copy number in SIV-infected and uninfected control macaques. Expression of FOXP3 in the ileal lamina propria was significantly decreased at all stages of infection compared to levels in uninfected control macaques. In addition, functional analysis of ileal CD4+ T cells from SIV-infected macaques revealed a lack of suppressive activity, suggestive of the absence of Tregs in that compartment. These results indicate that Tregs are rapidly depleted in the GALT of SIV-infected macaques defining a role for the loss of Treg-mediated suppression in the early events in the pathogenesis of the disease.
