Functional flexibility in T cells: independent regulation of CD4+ T cell proliferation and effector function in vivo.

Proliferation and differentiation of CD4+ T cells are often correlated, but it is not clear whether they are mechanistically linked. When antigen-specific T cells are present at high frequency in vivo, they all respond to antigenic peptide stimulation by expressing activation markers, but only a subset begins to proliferate. However, noncycling cells may synthesize the effector cytokine IFNgamma even though their cell cycle is blocked in G1. These data show that proliferation and effector function are not rigidly linked in T cells. Instead, CD4+ T cells have the flexibility to engage in or bypass clonal expansion based on the integration of multiple signals, including the frequency of other responding T cells.