Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection.
CD4+ CD25+ regulatory T cells (Tregs) suppress the activation and proliferation of effector lymphocytes. In human immunodeficiency virus type 1 (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 simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-1 disease. CD4+ T cells from the GALT, lymph nodes, and peripheral blood were isolated from SIV-infected pigtailed macaques on days 4, 14, and 114 postinoculation. Quantitative real-time reverse transcription-PCR was used to quantitate FOXP3 copy numbers 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 early events in the pathogenesis of the disease.
Chase
Amanda J
AJ
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sedaghat
Ahmad R
AR
German
Jennifer R
JR
Gama
Lucio
L
Zink
M Christine
MC
Clements
Janice E
JE
Siliciano
Robert F
RF
D000818:Animals; D001769:Blood / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008254:Macaca nemestrina; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012313:RNA