Cytotoxic and Helper T Cell Memory is Programmed by Mhc-Independent Generic Programs

The prevailing 'division of labor' concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets are present characterized by identical chemokine receptor expression signatures. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17+1 cells, expressed IL-6R but not SLAMF7, completely lacked cytotoxicity and instead displayed helper functions including CD40L expression. CD8+ helper T cells exhibited a unique TCR repertoire, expressed genes related to skin resident memory T cells (TRM) and were altered in the inflammatory skin disease psoriasis. Our findings provide evidence that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.