CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TCR and cytokines stimulation trigger CD39 expression and a phenotype associated to exhaustion in CD8+ T cells
Autor/es:
ABRATE C; RODRIGUEZ C; MONTES CL; BOSSIO S; GRUPPI A; BOCCARDO S; ACOSTA RODRIGUEZ EV
Lugar:
Tucuman
Reunión:
Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
TCR and cytokines stimulation trigger CD39 expression and a phenotype associated to exhaustion in CD8+ T cells.Carolina Abrate, Sabrina Bossio, Santiago Boccardo, Constanza Rodriguez, Adriana Gruppi, Eva Acosta Rodriguez, Carolina MontesDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.We demonstrated that tumor-infiltrating exhausted CD8+T cells exhibit high expression of CD39. These cells are absent in draining lymph node (dLN). Here, we aimed to identify signals capable to trigger exhaustion and CD39 expression on CD8+T cells. Purified CD8+T cells from dLN of B16F10-OVA tumor-bearing mice were stimulated with αCD3/αCD28 in presence of IL-6 and/or IL-27 (48hs). Then, cells were resting in IL-2 (24hs) and re-stimulated with αCD3/αCD28 (24hs). TCR stimulation increased the frequency of CD39+T cells which is even higher in presence of IL-27 or IL-6 plus IL-27 (p≤0.05 for all). A similar pattern was observed for the expression of PD-1 and TIM-3, however IL-6 and IL-27 triggered an increment of the frequency of PD-1+ and TIM-3+ respectively, respect to TCR-stimulated T cells (p≤0.05 for all). Interestingly these CD39+CD8+T cells exhibited co-expression of 2 or 3 inhibitory receptors (iRs): LAG-3, PD-1 and TIM-3. CD39+CD8+T cells express transcriptions factors (TF) associated with exhaustion such as EOMES, IRF-4 and TBET. In addition, we found that CD39+CD8+T cells were able to maintain IL-2, TNF and INF-y production compare with CD39-CD8+T cells. We next evaluate the expression of iRs and TF in CD8+T cells from dLN of B16F10-OVA tumor-bearing CD39KO mice stimulated following the protocol mentioned above. We observe that stimulated CD8+T cells from tumor-bearing CD39KO or WT mice show similar TFs and iRs expression. We conclude that TCR stimulation together with IL-6 or IL-27 trigger CD39 expression and phenotype associated to exhaustion. This phenomenon is not determined by the lack of CD39.Palabras Claves: Exhaustion, CD39, Lymphocyte CD8+, Tumor.