Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/40053

TitleEarly loss of splenic Tfh cells in SIV-infected rhesus macaques
Author(s)Moukambi, Félicien
Rabezanahary, Henintsoa
Rodrigues, Vasco
Racine, Gina
Robitaille, Lynda
Krust, Bernard
Andreani, Guadalupe
Soundaramourty, Calayselvy
Silvestre, Ricardo Jorge Leal
Laforge, Mireille
Estaquier, Jérôme
Issue date2015
PublisherPublic Library of Science (PLOS)
JournalPLoS Pathogens
Abstract(s)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.
TypeArticle
URIhttp://hdl.handle.net/1822/40053
DOI10.1371/journal.ppat.1005287
ISSN1553-7366
Publisher versionhttp://journals.plos.org/plospathogens/s/journal-information
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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