Research ArticleHIV

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

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Science Immunology  06 Apr 2018:
Vol. 3, Issue 22, eaan8884
DOI: 10.1126/sciimmunol.aan8884

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Zooming in on human lymph nodes

Follicular helper T cells (TFH) play an essential role in shaping B cell–mediated antibody responses. By obtaining lymph nodes from HIV+ individuals, Wendel et al. have used mass cytometry and TCR sequencing to directly examine the TFH response to HIV. They report that HIV infection alters the clonality of TFH cells with severe infections resulting in pronounced oligoclonal TFH responses. From a functional standpoint, they found that TFH cells in the lymph nodes of HIV+ individuals secreted interleukin-21 but were less polyfunctional as compared with TFH cells from healthy individuals and that this lack of polyfunctionality correlated with impaired isotype switching of B cells in the lymph nodes.

Abstract

Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits TFH 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 TFH cells in primary human LNs. We found evidence for intact antigen-driven clonal expansion of TFH cells and selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection, but the resulting TFH cells acquired an activation-related TFH cell signature characterized by interleukin-21 (IL-21) dominance. These IL-21+ TFH 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 TFH cells remain capable of responding to HIV antigens during chronic HIV infection but become functionally skewed and oligoclonally restricted under persistent antigen stimulation.

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