Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques

PLoS Pathogens

Jérôme Estaquier¹  Calayselvy Soundaramourty¹  Bernard Krust¹  Vasco Rodrigues¹  Henintsoa Rabezanahary²  Gina Racine²  Félicien Moukambi²  Guadalupe Andreani²  Lynda Robitaille²  Mireille Laforge³  Ricardo Silvestre⁴ 

[1] CNRS FR3636, Faculty of Medecine des Saint-Pères, Paris Descartes University, Paris, France;Centre Hospitalier Universitaire (CHU) de Québec Research Center, Faculty of Medecine, Laval University, Québec, Québec, Canada;ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal;Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

关键词: B cells;    Spleen;    SIV;    T helper cells;    Memory B cells;    T cells;    Cell differentiation;    Macaque;   

DOI  :  10.1371/journal.ppat.1005287

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY