Evaluation of the effect of proinflammatory cytokines in virtual memory CD8+ T cells.

LIDÓN NICOLAS; SAVID FRONTERA C; VIANO ME; FONTAINE Q; RODRIGUEZ GALÁN MC

Mar del Plata

Congreso; Reunión Conjunta SAIC ? SAI; 2022

SAI - SAIC

Virtual memory CD8+ T cells (TVM) are a subset of T cells with a memory phenotype (CD44hi and CD122hi) without previous antigen encounter. TVM can be distinguished from conventional memory T cells (TMEM) by their low expression of CD49d. We evaluated the role of different cytokines reported as important for both survival and functionality of TVM, such as IL-12, IL-18, IL-15, IL-4 and IFNgama.To determine the effect of IL-15 on TVM and TMEM survival, in vitro assays with variations in IL-15 concentrations demonstrated that the lowest IL-15 concentration (5ng/ml, IL-15lo) increased the percentage of TMEM, but this effect is not seen with the highest IL-15 concentration (20ng/ml, IL-15hi). Moreover, double stimulation with IL-15hi and plate-coated anti-CD3 induced a significant decrease in the number of TMEM. For TVM, both IL-15hi and the IL-15hi+anti-CD3 conditions induced the greatest increases in the percentage of this population.Regarding the possible functional activity of TVM, Fura-2 assays show that cells from lymph nodes in contact with KPC tumor cells induced higher intracellular calcium mobilization when they come from animals treated in vivo with IL-12 and IL-18 (enriched in TVM) compared to same cells from control mice (p<0,05).A potential effector molecule of TVM cells is NKG2D receptor. We evaluate the expression of this receptor in TVM and TMEM cells from IL4KO and IFNgammaKO mice in steady-state or IL-12+IL-18 in vivo stimulation. Our data demonstrate that the absence of IL-4 affects the expression (MFI) of NKG2D only in TMEM, while the absence of IFN affects the expression of NKG2D in both cell populations. Furthermore, the percentage of TVM cells that express NKG2D (% NKG2D+TVM) is not affected by the absence of both IL-4 and IFN, while the percentage of NKG2D+TMEM decreased in both KO mice.These results might contribute to understanding the potential involvement of TVM and TMEM cells in tumor growth control.