THE INDUCTION AND FUNCTIONS OF MURINE T-HELPER CELL SUBSETS

Through the release of distinct sets of cytokines, Th1 and Th2 cells exert characteristic and often mutually exclusive or antagonistic immune effector. functions, In the present report, we document and discuss several findings on the induction mechanisms of these cellular subtypes and present recent findings on their respective functions in vivo, The preferential induction of Th1 or Th2 cytokine patterns in mature CD4(+) T cells is generally attributed to the action of cytokines, In addition, there is evidence that prolonged T-cell receptor occupancy may induce the development of the Th2 phenotype, Prolonged occupancy of the T-cell receptor provides enough autocrine interleukin-4 to permit induction of the Th2 phenotype; Both Th1 and Th2 cells may be derived from a single mature CD4(+) T cell, providing strong evidence for post-thymic modulation of the T-cell cytokine profile and rendering the possibility of predetermined cytokine patterns in T cells unlikely, CD4(+) Th1 cells mediate the tumor necrosis factor- and interferon-gamma-dependent classic delayed type hypersensitivity reaction, We found that Th2 cells were also capable of mediating local inflammatory reactions that depended on their prototypic lymphokine interleukin-4, and, in high tumor necrosis factor-producing mouse strains, upon tumor necrosis factor-alpha. Both Th-cell subsets induced cellular infiltrates that were not distinguishable on histologic grounds, In contrast to the widely accepted belief that only Th1 cells can mediate delayed hypersensitivity reactions, our results demonstrate that T cells with either lymphokine profile can cause tissue inflammation with leukocytic infiltrates.