GAMMA-DELTA T-CELL HELP IN RESPONSES TO PATHOGENS AND IN THE DEVELOPMENT OF SYSTEMIC AUTOIMMUNITY

Mice rendered deficient in alpha beta T-cells by single-gene knockout mutation show enhanced levels of autoantibody formation and even some symptoms of autoimmune disease. This is remarkable given that most exp erimental studies heretofore have indicated that the development of au toimmune disease is highly multigenic, requiring the complementary act ions of multiple loci. The basis of the phenomenon in alpha beta T-cel l-deficient mice appears to be the provision of help to B-cells by oth er cells, including gamma delta T-cells. Perhaps surprisingly, gamma d elta T-cell help seems quite efficacious, particularly after infection , when it can culminate in the formation of germinal centers. Furtherm ore, two independent sets of studies reviewed here indicate that signi ficant levels of self-reactive IgG can also be provoked by gamma delta T-cells independent of germinal center formation. The task ahead is t o integrate this pathway into the physiologic immune responses of heal thy individuals, immunocompromised individuals, and newborns.