title: Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.
abstract: 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.
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.
authors.forename: Félicien
authors.initials: F
authors.lastname: Moukambi
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.
authors.forename: Henintsoa
authors.initials: H
authors.lastname: Rabezanahary
authors.affiliation: CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France.
authors.forename: Vasco
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.
authors.forename: Gina
authors.initials: G
authors.lastname: Racine
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.
authors.forename: Lynda
authors.initials: L
authors.lastname: Robitaille
authors.affiliation: CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Krust
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Andreani
authors.affiliation: CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France.
authors.forename: Calayselvy
authors.initials: C
authors.lastname: Soundaramourty
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.affiliation: CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Laforge
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada.|CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
mesh_terms: D000818:Animals; D002469:Cell Separation; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*