CD8+ T cells up-regulate CD39 expression and inhibitory receptors upon in vitro TCR and cytokines stimulation

ABRATE C; BOSSIO S; CANALE F; RODRIGUEZ C; GRUPPI A; ACOSTA RODRIGUEZ EV; MONTES CL

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; 2018

SAI

Previously we have shown that the frequency of exhausted CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. We aimed to evaluate signals that may influence CD39 and inhibitory receptors (IRc) upregulation on CD8+ T cells. Purified CD8+ T cells from draining lymph node of B16F10-OVA tumor bearing mice were stimulated during 48hs with αCD3/αCD28 in presence or absence of IL-6 or conditioned medium (CM) obtained by culturing tumors from B16F10-OVA bearing mice. Then cells were resting in IL-2 (96hs) and re-stimulated with αCD3/αCD28 (24hs). We observed that after TCR stimulation, the frequency of CD39+ and PD-1+TIM-3+ CD8+T cells were (27.3%±8.1% and 50.57%±0.46% respectively), however the frequency of both populations was not increase by neither MC nor IL-6. Next we stimulated the CD8+ T cells reducing the resting with IL-2 (24hs) in presence or absence of IL-6, IL-27 or CM. We found that TCR stimulation increased significantly the % of CD39+CD8+ T cells (p≤0.05) respect to non-stimulated cells, and the frequency of the CD39+ expressing cells decreased in absence of IL-2 (p≤0.05). The stimulation with cytokines associated with exhaustion such as IL-27 or a combination of IL-6/IL-27 increased the frequency of CD39+ cells (p