Human CD4+ T cell differentiation and effector function: implications for autoimmunity.

Human CD4+ memory T cells progress through stages of postthymic differentiation that have been characterized by distinct phenotypes. We have investigated the factors regulating cytokine production, and the correlation between phenotype and effector function in normal and autoimmune individuals. These studies suggest that antigen-induced proliferation in the periphery drives CD4+ T cells through successive stages of differentiation that culminate in optimal effector function and resistance to external modulatory influences. Moreover, these studies support the concept that in autoimmune individuals, the chronic accumulation of differentiated proinflammatory T cells perpetuate the inflammatory response resulting in aggressive disease.