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Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection
The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4(+) memory T cell (T(M)) homeostasis. CD4(+) naive T cells (T(N)) also decline in these infections, but their contribution to disease progression is less clear. W...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328373/ https://www.ncbi.nlm.nih.gov/pubmed/22451717 http://dx.doi.org/10.1084/jem.20112071 |
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author | Okoye, Afam A. Rohankhedkar, Mukta Abana, Chike Pattenn, Audrie Reyes, Matthew Pexton, Christopher Lum, Richard Sylwester, Andrew Planer, Shannon L. Legasse, Alfred Park, Byung S. Piatak, Michael Lifson, Jeffrey D. Axthelm, Michael K. Picker, Louis J. |
author_facet | Okoye, Afam A. Rohankhedkar, Mukta Abana, Chike Pattenn, Audrie Reyes, Matthew Pexton, Christopher Lum, Richard Sylwester, Andrew Planer, Shannon L. Legasse, Alfred Park, Byung S. Piatak, Michael Lifson, Jeffrey D. Axthelm, Michael K. Picker, Louis J. |
author_sort | Okoye, Afam A. |
collection | PubMed |
description | The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4(+) memory T cell (T(M)) homeostasis. CD4(+) naive T cells (T(N)) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4(+) T(N) in SIV pathogenesis using rhesus macaques (RMs) selectively and permanently depleted of CD4(+) T(N) before SIV infection. CD4(+) T(N)-depleted and CD4(+) T(N)-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4(+) T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4(+) T(M) recovery, only sham-treated RMs reconstituted CD4(+) T(N). CD4(+) T(N)-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4(+) T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8(+) T cell responses. However, CD4(+) T(N)-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4(+) T(N) deficiency had no significant effect on CD4(+) T(M) homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4(+) T(N) compartment is dispensable for CD4(+) T(M) homeostasis in progressive SIV infection, and they confirm that CD4(+) T(M) comprise a homeostatically independent compartment that is intrinsically capable of self-renewal. |
format | Online Article Text |
id | pubmed-3328373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33283732012-10-09 Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection Okoye, Afam A. Rohankhedkar, Mukta Abana, Chike Pattenn, Audrie Reyes, Matthew Pexton, Christopher Lum, Richard Sylwester, Andrew Planer, Shannon L. Legasse, Alfred Park, Byung S. Piatak, Michael Lifson, Jeffrey D. Axthelm, Michael K. Picker, Louis J. J Exp Med Brief Definitive Report The development of AIDS in chronic HIV/simian immunodeficiency virus (SIV) infection has been closely linked to progressive failure of CD4(+) memory T cell (T(M)) homeostasis. CD4(+) naive T cells (T(N)) also decline in these infections, but their contribution to disease progression is less clear. We assessed the role of CD4(+) T(N) in SIV pathogenesis using rhesus macaques (RMs) selectively and permanently depleted of CD4(+) T(N) before SIV infection. CD4(+) T(N)-depleted and CD4(+) T(N)-repleted RMs were created by subjecting juvenile RMs to thymectomy versus sham surgery, respectively, followed by total CD4(+) T cell depletion and recovery from this depletion. Although thymectomized and sham-treated RMs manifested comparable CD4(+) T(M) recovery, only sham-treated RMs reconstituted CD4(+) T(N). CD4(+) T(N)-depleted RMs responded to SIVmac239 infection with markedly attenuated SIV-specific CD4(+) T cell responses, delayed SIVenv-specific Ab responses, and reduced SIV-specific CD8(+) T cell responses. However, CD4(+) T(N)-depleted and -repleted groups showed similar levels of SIV replication. Moreover, CD4(+) T(N) deficiency had no significant effect on CD4(+) T(M) homeostasis (either on or off anti-retroviral therapy) or disease progression. These data demonstrate that the CD4(+) T(N) compartment is dispensable for CD4(+) T(M) homeostasis in progressive SIV infection, and they confirm that CD4(+) T(M) comprise a homeostatically independent compartment that is intrinsically capable of self-renewal. The Rockefeller University Press 2012-04-09 /pmc/articles/PMC3328373/ /pubmed/22451717 http://dx.doi.org/10.1084/jem.20112071 Text en © 2012 Okoye et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Okoye, Afam A. Rohankhedkar, Mukta Abana, Chike Pattenn, Audrie Reyes, Matthew Pexton, Christopher Lum, Richard Sylwester, Andrew Planer, Shannon L. Legasse, Alfred Park, Byung S. Piatak, Michael Lifson, Jeffrey D. Axthelm, Michael K. Picker, Louis J. Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title | Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title_full | Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title_fullStr | Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title_full_unstemmed | Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title_short | Naive T cells are dispensable for memory CD4(+) T cell homeostasis in progressive simian immunodeficiency virus infection |
title_sort | naive t cells are dispensable for memory cd4(+) t cell homeostasis in progressive simian immunodeficiency virus infection |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328373/ https://www.ncbi.nlm.nih.gov/pubmed/22451717 http://dx.doi.org/10.1084/jem.20112071 |
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