CD32+CD4+ T cells sharing B cell properties increase in lymphoid tissues during simian immunodeficiency virus infection

HIV reservoirs in tissues form the major hurdle to an HIV cure. Despite major progress made on the understanding of the establishment and persistence of viral reservoirs, the characterization of composition and dynamics of the viral reservoir is still uncomplete. In addition, most studies in HIV infection are limited to blood. Here we take advantage of non-human primate models to provide a longitudinal analysis on potential viral target cells in distinct body compartments : blood, lymph nodes (LN), spleen ileum, jejunum and liver. We observed an increase in CD32+CD4+ T cells in secondary lymphoid tissues and intestine during primary and chronic pathogenic SIVmac infection. In the natural host (African green monkey, AGM), increase of the CD4+CD32+T cell levels was observed in tissues with higher replication and immune activation. CD32+CD4+ T cells expressed more often markers associated with HIV infected and/or reservoir cells (PD-1, CXCR5 for TFH cells in SLT, and CXCR3 for Th1 cells) than CD32- cells. The tissue CD32+CD4+T cells displayed higher levels of actively transcribed SIV RNA than CD32-CD4+T cells. The genome-wide transcriptome of CD32+CD4+ T cells in spleen from SIV-infected animals indicated that the CD32+CD4+ T cells shared B cell markers. The CD20+ expressing CD32+CD4+ T cells were increased in the tissues but not in the blood during SIV infection. Altogether, the study showed that SIV infection increases the frequencies of CD32+CD4+ T cells in tissues more than in blood. These cells might represent a not well-described subpopulation of activated CD4+ T cells. Transcriptome profiling of different T4 lymphocyte subsets according to CD32 expression in the spleen of pathogenic and nonpathogenic simian models of SIV infection