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

Amanda J. Chase, Ahmad R. Sedaghat, Jennifer R. German, Lucio Gama, Mary Christine Zink, Janice E Clements, Robert F Siliciano

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12748-12757
Number of pages10
JournalJournal of Virology
Volume81
Issue number23
DOIs
StatePublished - Dec 2007

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
laminae (animals)
Macaca
Virus Diseases
lymph nodes
Mucous Membrane
T-lymphocytes
Lymph Nodes
Human immunodeficiency virus 1
HIV-1
blood
T-Lymphocytes
Lymphoid Tissue
infection
Macaca nemestrina
digestive system
cells
Regulatory T-Lymphocytes
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "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",
abstract = "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.",
author = "Chase, {Amanda J.} and Sedaghat, {Ahmad R.} and German, {Jennifer R.} and Lucio Gama and Zink, {Mary Christine} and Clements, {Janice E} and Siliciano, {Robert F}",
year = "2007",
month = "12",
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T1 - 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

AU - Chase, Amanda J.

AU - Sedaghat, Ahmad R.

AU - German, Jennifer R.

AU - Gama, Lucio

AU - Zink, Mary Christine

AU - Clements, Janice E

AU - Siliciano, Robert F

PY - 2007/12

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N2 - 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.

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