Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy

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Abstract

Background: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4+ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4+ memory subsets or lost and fail to regenerate during ART. Methods: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results: Changes in proliferative CD4+ memory subsets during infection accelerated their depletion. This reduced the central memory CD4+ T-cell pool and contributed to slow CD4+ T-cell restoration during ART. Conclusion: There was a lack of restoration of the CD4+ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalJournal of Medical Primatology
Volume36
Issue number4-5
DOIs
StatePublished - Aug 2007

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Virus Diseases
T-lymphocytes
T-Lymphocytes
therapeutics
infection
T-Lymphocyte Subsets
Therapeutics
Lymphoid Tissue
Macaca mulatta
Viral Load
Real-Time Polymerase Chain Reaction
viral load
Blood Cells
Homeostasis
homeostasis
quantitative polymerase chain reaction
digestive system
Infection

Keywords

  • Antiretroviral therapy
  • Central memory
  • Gut-associated lymphoid tissue
  • Memory homeostasis
  • Simian immunodiciency virus

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

@article{343fbffcd54e436f897ef4eee8b3c962,
title = "Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy",
abstract = "Background: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4+ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4+ memory subsets or lost and fail to regenerate during ART. Methods: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results: Changes in proliferative CD4+ memory subsets during infection accelerated their depletion. This reduced the central memory CD4+ T-cell pool and contributed to slow CD4+ T-cell restoration during ART. Conclusion: There was a lack of restoration of the CD4+ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.",
keywords = "Antiretroviral therapy, Central memory, Gut-associated lymphoid tissue, Memory homeostasis, Simian immunodiciency virus",
author = "D. Verhoeven and Sumathi Sankaran-Walters and Satya Dandekar",
year = "2007",
month = "8",
doi = "10.1111/j.1600-0684.2007.00239.x",
language = "English (US)",
volume = "36",
pages = "219--227",
journal = "Journal of Medical Primatology",
issn = "0047-2565",
publisher = "Blackwell Munksgaard",
number = "4-5",

}

TY - JOUR

T1 - Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy

AU - Verhoeven, D.

AU - Sankaran-Walters, Sumathi

AU - Dandekar, Satya

PY - 2007/8

Y1 - 2007/8

N2 - Background: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4+ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4+ memory subsets or lost and fail to regenerate during ART. Methods: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results: Changes in proliferative CD4+ memory subsets during infection accelerated their depletion. This reduced the central memory CD4+ T-cell pool and contributed to slow CD4+ T-cell restoration during ART. Conclusion: There was a lack of restoration of the CD4+ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

AB - Background: Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4+ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4+ memory subsets or lost and fail to regenerate during ART. Methods: Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results: Changes in proliferative CD4+ memory subsets during infection accelerated their depletion. This reduced the central memory CD4+ T-cell pool and contributed to slow CD4+ T-cell restoration during ART. Conclusion: There was a lack of restoration of the CD4+ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

KW - Antiretroviral therapy

KW - Central memory

KW - Gut-associated lymphoid tissue

KW - Memory homeostasis

KW - Simian immunodiciency virus

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