PVR–CD226 interaction regulates IL-10 production during human T cell differentiation

Presence of plate-bound PVR or nectin-2 at 2 µg/mL did not significantly modify cell viability nor frequency of proliferating cells compared to isotype control. As expected, Treg conditions significantly increased FoxP3 expression (paired T test p<0.0001, n=6) which was accompanied by elevation of CD226 levels (p=0.0026). Surprisingly, Treg conditions led to reduction of TIGIT expression (p=0.0039) and CD96 (p=0.084). In addition, PVR ligation resulted in a higher frequency of IL10-producing cells in Th0 conditions (p=0.0193), most of them expressing high levels of CD226 (78.48% ± 2.324), CD96 (59.87% ± 4.032), and to a lesser extent, TIGIT (39.82% ± 4.043). Consistently, under these experimental conditions dual blockade of TIGIT and CD96 did not abrogate the increase in the percentage of IL-10 producing cells, suggesting that PVR binds CD226 expressing cells to upregulate IL-10 production.