Analysis of Butyrophilin-Mediated Activation of y8 T Cells from Human Spleen

There is considerable interest in therapeutically engaging human y8 T cells. However, due to the unique TCRs of human y8 T cells, studies from animal models have provided limited directly applicable insights, and human y8 T cells from key immunological tissues remain poorly characterized. In this study, we investigated y8 T cells from human spleen tissue. Compared to blood, where V82+Vy9+ Intracellular cytokine staining revealed that IFN-y was produced by a substantial fraction of splenic y8 T cells, IL-17A by a small generally little expression of natural cytotoxicity receptors, TIM-3, LAG-3, or killer Ig-like receptors. In vitro expansion was associated and V81+Vy9+ T cells were capable of responding to the extracellular domain of BTN2A1, whereas the addition of BTN3A1 only markedly enhanced the responses of V82+Vy9+ T cells. Conversely, V81+Vy9+ T cells appeared more responsive than V82+Vy9+ T cells may segregate target cell responses of V82+Vy9+ and V81+Vy9+ T cells. The Journal of Immunology, 2024,212: 284-294.