Suppressive activity of V?2+ ?? T cells on ?? T cells is licensed by TCR signaling and correlates with signal strength.

ABSTRACT: Despite recent progress in the understanding of ?? T cells' roles and functions, their interaction with ?? T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral V?2+ T cells with immunosuppressive function on autologous ?? T cells. We found that negatively freshly isolated V?2+ T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, V?2+ T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on ?? T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of V?2+ T cells. This indicates that V?2+ T cells' suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. V?2+ T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of V?2+ T cells via the V?2 TCR for activation and expansion induces V?2+ T cells' potent killer activity while simultaneously licensing them to suppress ?? T cell responses. Taken together, the study is a further step to understand-in more detail-the suppressive activity of V?2+ ?? T cells.

SUBMITTER: Schilbach K 

PROVIDER: S-EPMC7113223 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature