Mechanisms Underlying Lineage Commitment and Plasticity of Helper

CD4+ T cells are critical for host defense but are also major drivers of immune-mediated disease. These T cells specialize to become distinct subsets and produce restricted patterns of cytokines, which are tailored to combat various microbial pathogens. Although classically viewed as distinct lineages, recent work calls into question whether helper CD4+ T cell subsets are more appropriately viewed as terminally differentiated cells or works in progress. Herein, we review recent advances that pertain to this topic and the mechanisms that contribute to helper CD4+ T cell commitment and plasticity. The therapeutic implications of these new findings are also considered. Faced with innumerable microbial patho-gens, antigen-inexperienced naïve CD4+T cells orchestrate immune responses by differentiating into T helper (TH) cell popula-tions that secrete distinct sets of cytokines. In this manner, they tailor their responses to the character of the threat encountered, providing help to B lymphocytes and CD8+ cytotoxic Tcells and activating the cells of the innate immune system. The importance of CD4+ Tcells is vividl