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

LIDON, NICOLÁS LEONEL; SAVID-FRONTERA, CONSTANZA; VIANO, MARIA ESTEFANIA; FONTAINE, QUENTIN; RODRIGUEZ-GALAN, MARIA CECILIA

Mar del Plata

Congreso; Reunión anual de sociedades de biociencias SAIC. SAI. SAFIS; 2022

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 IFNg. To determine the effect of IL-15 on TVM and TMEM survival, in vitro assayswith 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 comefrom 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 evaluated the expression of this receptor in TVM and TMEM cells from IL4KO and IFNgKO 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 IFNg 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 IFNg, while the percentageof 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.