Functional subsets of CD4 T cells. Naïve CD4 T cells – that is, T cells that have not yet been activated by antigen – circulate in the blood and lymph until they are activated, usually by dendritic cells, which are specialized for that function. They then proliferate and differentiate into different functional subsets, distinguished by the different cytokines they produce (indicated under each CD4 T cell type): the cytokines act on other immune cells, activating them in turn. The four known subsets of CD4 T cells are T_H1 cells, which induce infl ammatory responses that protect the tissues; T_H2 cells, which are largely responsible for protecting the epithelial surfaces of the gut, lung and genitourinary system; T_H17 cells, which produce early infl ammatory responses; and T_REG cells, which inhibit the responses of the other cell types and are thought to provide protection from autoimmune disease. IFN, interferon; IL, interleukin, NK, natural killer; TGF, transforming growth factor. Modifi ed from Figure 5–22 in DeFranco AL, Locksley RM, Robertson M: Immunity: The Immune Response in Infectious and Infl ammatory Disease. London: New Science Press; 2007.