COSTIMULATORY SIGNALS CAN SELECTIVELY MODULATE CYTOKINE PRODUCTION BYSUBSETS OF CD4(-CELLS() T)

Analysis of experimental animal models and human clinical samples has indicated that the selective activation of CD4(+) T cell subsets with distinct profiles of cytokine production plays an important role in th e pathogenesis of human inflammatory and allergic diseases. The possib ility that differential activation of costimulatory pathways is a mech anism for selectively modulating cytokine production by CD4(+) T cells was tested. The proliferative response and cytokines secreted by a pa nel of human CD4(+) T cell clones, representative of Th1 or Th2/0 cell s, in response to activation of different costimulatory pathways was m easured. CD28-mediated costimulatory signals induced proliferation and lFN-gamma secretion by Th1 cells. Although CD28-ligation induced Th2/ 0 cells to proliferate, it did not trigger IL-4 production. Ligation o f LFA-1 and CD45 isoforms also generated costimulatory signals activat ing cytokine secretion by the different types of T cell clones. Th1 ce lls secreted the same profile of cytokines, irrespective of which cost imulatory pathway was engaged. However, the cytokines secreted by a su bset of Th2/0 cells varied, depending upon which costimulatory pathway s were activated. These results suggest that the costimulatory pathway s activated by APCs can selectively influence cytokine production by C D4(+) T cell subsets.