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 (T _FH ) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5 ^- CD4 ⁺ T cells with T _FH -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 T _FH 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.
(Published by Elsevier Inc.)