Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.
Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact...
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2015-12-01
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doaj-02cb8889eb034f64b27ad3d64662f0782020-11-25T01:58:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-12-011112e100528710.1371/journal.ppat.1005287Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.Félicien MoukambiHenintsoa RabezanaharyVasco RodriguesGina RacineLynda RobitailleBernard KrustGuadalupe AndreaniCalayselvy SoundaramourtyRicardo SilvestreMireille LaforgeJérôme EstaquierFollicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.http://europepmc.org/articles/PMC4671657?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Félicien Moukambi Henintsoa Rabezanahary Vasco Rodrigues Gina Racine Lynda Robitaille Bernard Krust Guadalupe Andreani Calayselvy Soundaramourty Ricardo Silvestre Mireille Laforge Jérôme Estaquier |
spellingShingle |
Félicien Moukambi Henintsoa Rabezanahary Vasco Rodrigues Gina Racine Lynda Robitaille Bernard Krust Guadalupe Andreani Calayselvy Soundaramourty Ricardo Silvestre Mireille Laforge Jérôme Estaquier Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. PLoS Pathogens |
author_facet |
Félicien Moukambi Henintsoa Rabezanahary Vasco Rodrigues Gina Racine Lynda Robitaille Bernard Krust Guadalupe Andreani Calayselvy Soundaramourty Ricardo Silvestre Mireille Laforge Jérôme Estaquier |
author_sort |
Félicien Moukambi |
title |
Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. |
title_short |
Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. |
title_full |
Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. |
title_fullStr |
Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. |
title_full_unstemmed |
Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques. |
title_sort |
early loss of splenic tfh cells in siv-infected rhesus macaques. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2015-12-01 |
description |
Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies. |
url |
http://europepmc.org/articles/PMC4671657?pdf=render |
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