THE INDUCTION AND FUNCTIONS OF MURINE T-HELPER CELL SUBSETS

Through the release of distinct sets of cytokines, Th1 and Th2 cells e xert characteristic and often mutually exclusive or antagonistic immun e effector. functions, In the present report, we document and discuss several findings on the induction mechanisms of these cellular subtype s and present recent findings on their respective functions in vivo, T he preferential induction of Th1 or Th2 cytokine patterns in mature CD 4(+) T cells is generally attributed to the action of cytokines, In ad dition, there is evidence that prolonged T-cell receptor occupancy may induce the development of the Th2 phenotype, Prolonged occupancy of t he T-cell receptor provides enough autocrine interleukin-4 to permit i nduction of the Th2 phenotype; Both Th1 and Th2 cells may be derived f rom a single mature CD4(+) T cell, providing strong evidence for post- thymic modulation of the T-cell cytokine profile and rendering the pos sibility of predetermined cytokine patterns in T cells unlikely, CD4() Th1 cells mediate the tumor necrosis factor- and interferon-gamma-de pendent 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 hi gh tumor necrosis factor-producing mouse strains, upon tumor necrosis factor-alpha. Both Th-cell subsets induced cellular infiltrates that w ere not distinguishable on histologic grounds, In contrast to the wide ly accepted belief that only Th1 cells can mediate delayed hypersensit ivity reactions, our results demonstrate that T cells with either lymp hokine profile can cause tissue inflammation with leukocytic infiltrat es.