Mapping the Lineage Relationship between CXCR5+ and CXCR5- CD4+ T Cells in HIV-Infected Human Lymph Nodes.
CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5- CD4+ T cells with TFH-cell-like features. This CXCR5- subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5-PD-1+ICOS+ T cells revealed a shared clonal relationship with TFH cells. CXCR5-PD-1+ICOS+ T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5-PD-1+ICOS+ T cells to circulating CXCR5- CD4+ T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation.
['Del Alcazar|Daniel|D|', 'Wang|Yifeng|Y|', 'He|Chenfeng|C|', 'Wendel|Ben S|BS|', 'Del Río-Estrada|Perla M|PM|', 'Lin|Jerome|J|', 'Ablanedo-Terrazas|Yuria|Y|', 'Malone|Michael J|MJ|', 'Hernandez|Stefany M|SM|', 'Frank|Ian|I|', 'Naji|Ali|A|', 'Reyes-Terán|Gustavo|G|', 'Jiang|Ning|N|', 'Su|Laura F|LF|']
D001402:B-Lymphocytes D015496:CD4-Positive T-Lymphocytes D005260:Female D015658:HIV Infections D015497:HIV-1 D006801:Humans D008198:Lymph Nodes D008297:Male D054380:Receptors, CXCR5
human lymph node HIV infection chronic inflammation T-bet+ B cells follicular helper T cells mass cytometry migration