IL-21, inflammatory cytokines and hyper polarized CD8⁺T cells are central players in Lupus immune pathology

Abstract

Systemic Lupus Erythematous (SLE) is a chronic autoimmune disorder, broadly characterized by systemic inflammation along with heterogeneous clinical manifestations, severe morbidity, moribund organ failure and eventual mortality. In our study, SLE patients displayed higher percentage of activated, inflamed and hyper polarized CD8+ T cells, dysregulated CD8+ T cell differentiation, significantly elevated serum inflammatory cytokines, higher accumulation of cellular ROS when compared to healthy controls. Importantly, these hyper inflammatory/hyper polarized CD8+ T cells responded better to an anti-oxidant than to an oxidant. Terminally differentiated Tc1 cells also showed plasticity upon Oxidant/antioxidant treatment but was in contrast to the SLE CD8+ T cell response. Our studies suggest that the differential phenotype and redox response of SLE CD8+ T cells and Tc1 cells could be attributed to their cytokine environs during their respective differentiation and eventual activation environs. Polarisation of Tc1 cells with IL-21 drove hyper cytoxicity without hyper polarisation suggesting that SLE inflammatory environment could drive the extreme aberrancy in SLE CD8+ T cell.