In vivo priming of CD4 T cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-gamma, and can subsequently differentiate into IL-4- or IFN-gamma-secreting cells

The differentiation of antigen-stimulated naive CD4 T cells into T helper ( Th)1 or Th2 effector cells can be prevented in vitro by transforming growth factor (TGF)-beta and anti-interferon (IFN)-gamma, These cells proliferate and synthesize interleukin (IL)-2 but not IFN-gamma or 1L-4, and can diffe rentiate into either Th1 or Th2 cells. We have now, used two-color Elispots to reveal substantial numbers of primed cells producing IL-2 but not IL-4 or IFN-gamma during the Th1- or Th2-biased immune responses induced by solu ble proteins or with adjuvants. These cells were CD4(+)CD44(high) and were present during immediate and long-term immune responses of normal mice. Nai ve T cell receptor for antigen (TCR) transgenic (DO11.10) T cells were prim ed in vivo after adoptive transfer into normal hosts and FACS (R) cloned un der conditions that did not allow further differentiation. After clonal. pr oliferation, aliquots of each clone were cultured in Th1- or Th2-inducing c onditions. Many in vivo-primed cells were uncommitted, secreting IL-2 but n ot IL-4 or IFN-gamma at the first cloning step, but secreting either IL-4 o r IFN-gamma after differentiation in the appropriate conditions. These in v ivo-primed, uncommitted, IL-2-producing cells may constitute an expanded po ol of antigen-specific cells that provide extra flexibility for immune resp onses by differentiating into Th1 or Th2 phenotypes later during the same o r subsequent immune responses.