The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes.

Follicular helper CD4 ⁺ T cells (T _FH ) play an integral role in promoting B cell differentiation and affinity maturation. Whereas T _FH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits T _FH responses in LNs remains unclear. Advances in this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry with T cell receptor repertoire sequencing to interrogate the composition of T _FH cells in primary human LNs. We found evidence for intact antigen-driven clonal expansion of T _FH cells and selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection, but the resulting T _FH cells acquired an activation-related T _FH cell signature characterized by interleukin-21 (IL-21) dominance. These IL-21 ⁺ T _FH cells contained an oligoclonal HIV-reactive population that preferentially accumulated in patients with severe HIV infection and was associated with aberrant B cell distribution in the same LN. These data indicate that T _FH cells remain capable of responding to HIV antigens during chronic HIV infection but become functionally skewed and oligoclonally restricted under persistent antigen stimulation.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)