SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells

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 exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17+1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8(+) helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (T-RM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4(+) and CD8(+) T cell capabilities and functions in human health and disease needs to be revised. We classically consider the T cell compartment divided into cytotoxic CD8(+)T cells and multiple, different helper CD4(+)T cell subsets. Here the authors demonstrate that distinct memory CD8(+)T cell subsets phenotypically inhabit CD4(+)T cell like populations including some with helper-like characteristics.