Critical Role of CD28/B7 Costimulation in the Development of Human

CD28 is a major costimulatory signal receptor for T cells. We have used human naive CD4+ cells from cord blood to ana-lyze the effect of the CD28/67 costimulatory pathway on development of T helper (Th) subsets. We show that CD28 costimulation is critical for development of the Th2 cytokine-producing cells and that in the absence of CD28 costimula-tion, cells are not primed to produce Th2 cytokines and con-sequently "default " to the Thl subset, independent of the HELPER (Th) cells play a critical role in immune responses, which depend largely on their production of cytokines. Studies of both murine and human cloned CD4+ cells have shown a dichotomy in Th cytokine produc-tion and so Th cells are currently categorized into two major subsets, namely Thl and Th2.1-4 The Thl subset produces interleukin-2 (IL-2), interferon-y (IFN-y), tumor necrosi