Relative abilities of 4-1BB (CD137) and CD28 to co-stimulate the response of cytokine deflected Th1 and Th2 cells.

In this report we show that allo-stimulated naïve CD4+ cells when cultured in IL-2, IFN-gamma, IL-12 and anti-IL-4 differentiated into Th1 cells expressing very low amounts of 4-1BB molecule, but high amounts of CD28. By contrast, allo-stimulated naive CD4+ cells cultured in the presence of exogenous IL-2, IL-10, IL-4 and anti-INF-gamma evolved into Th2 expressing high amounts of both 4-1BB and CD28. Various Th1/Th2 clones derived from limiting dilution also exhibited similar expression pattern. This differential expression of co-stimulatory molecules on Th subsets account for the ability of 4-1BB to trigger both the proliferation and production of IL-4 by Th2 cells only and for the ability of CD28 to trigger proliferation and typical secretion in both Th1 and Th2 cells.