GITR, 41BB and PD1 expression on CD8+ T cells from people living with HIV: An initial characterization to evaluate different functional reprograming strategies through GITR-mediated costimulation.

ALEJANDRO CZERNIKIER; LUCIA BAQUERO; YANINA GHIGLIONE; NATALIA LAUFER; MARIA FERNANDA PASCUTTI; GABRIELA TURK

La Serena

Congreso; XLIV Reunión Anual SOMICH 2022; 2022

Sociedad de Microbiología de Chile (SOMICH)

BackgroundA robust CD8+ T-cell response is key for the development of therapies capable to achieve asustained ART-free HIV remission. Costimulation through GITR and 41BB pathways enhancethe effector function of CD8+ T cells (CD8TCs), representing a putative strategy to restore cellexhaustion. However, little is known about the expression of these molecules on HIV-specificCD8TCs. Here, we evaluated the level of expression of GITR, 41BB and PD-1 on bulk and HIVspecific CD8TCs obtained from people living with HIV (PLWH) and also the effect of a novelantiGITR agonist on HIV-specific CD8TC functionality.MethodsTwenty-two HIV+ subjects were enrolled, eleven before starting ART and eleven under ART.PBMCs were purified from blood samples and stimulated with HIV peptide pools. GITR, 41BBand PD1 expression was analyzed on bulk and HIV-specific CD8TCs and also across memorysubsets (naïve, CM, EM and TE) by flow cytometry. Additionally, PMBCs from one on-ARTparticipant were expanded for 5 days with HIV peptides plus a GITR agonist. CD107a/b, IFN-and TNF- production was studied by flow cytometry. Data was analyzed using non-parametricstatistics.ResultsRegarding participants off-ART, GITR, 41BB and PD1 expression were significantly higher onHIV-specific CD8TCs (26.3%, 69.6%, 64.4%) compared to bulk CD8TCs (1.05%, 3.56%, 11.10%,respectively; p