Accidental poisoning with Malathion.

Abstract

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesion molecule expressed on the surface of naïve, effector, and memory CD4⁺ and CD8⁺ T cells. We identified PSGL-1 to be an immune checkpoint inhibitor as antibody-mediated ligation of PSGL-1 promotes T cell exhaustion and deletion of PSGL-1 prevents chronic viral infection and inhibits tumor. To investigate the role of PSGL-1 signaling in the development of T cell responses, we assessed the differentiation state, expansion capacity, and glycolytic profile of PSGL-1-deficient T cells. PSGL-1^+/− OT-II CD4⁺ T cells demonstrated increased skewing towards IL-17A⁺ T cells compared to wild-type OT-II CD4⁺ T cells under T_H17 conditions, and reduced IFNg⁺ cells under both T_H0 and T_H1 conditions. In a B16-OVA tumor model, we observed increased IL-13⁺ CD4⁺ T cells among the intratumoral T cell compartment in PSGL-1^−/− mice. <i>In vitro</i> activation with a sub-optimal dose of αCD3 of PSGL-1^−/− OT-II CD4⁺ T cells demonstrated increased expansion and expression of CD25 compared to wild-type OT-II CD4⁺ T cells. Further, adoptively transferred <i>in vitro</i>-activated PSGL-1^−/− CD4⁺ T cells demonstrated greater expansion <i>in vivo</i> upon adoptive transfer into RAG^−/− host mice. Using the Seahorse glycolysis stress test, we identified that both CD4⁺ and CD8⁺ PSGL-1^−/− T cells demonstrate increased glycolysis after 72 hours of <i>in vitro</i> activation compared to wild-type T cells. Further, <i>in situ</i> activation of PSGL-1^−/− CD8⁺ T cells demonstrates that at both sub-optimal and optimal levels of αCD3 stimulation, PSGL-1^−/− CD8⁺T cells have increased glycolysis and increased glycolytic capacity. Taken together, these data show that PSGL-1 signaling has an intrinsic and immediate role in the development of T cell responses.