Autoimmunity: increasing suspects in the CD4+ T cell lineup

Chronic reactivity of CD4(+) T cells to autoantigens and to components of the commensal flora drive destructive inflammation in a variety of mouse models of autoimmunity. Insight gained using these models is empowering translational research into human disease. Immunologists are trying to assign disease culpability to one of the ever-growing number of T helper (T(H)) cell subsets. Although recent discovery of the interleukin 17-producing T(H)-17 lineage appeared to supplant the pre-eminence of T(H)1 cells in promoting autoimmunity, the newest data defy simple paradigms. Here we speculate on the respective contributions to autoimmunity made by an increasingly complex list of T(H) subsets and argue that the T(H)1 phenotype may be staging a comeback.