A call to arms: the cytokine selection service.

The process by which naïve T helper (T(H)) cells differentiate into the T(H)1 and T(H)2 subtypes has been well studied. However, there remain some unresolved issues pertaining to the requirements for the initial step of T(H) cell differentiation. Much debate exists about whether the roles of cytokines include the forcing of the initial steps of differentiation on naïve T(H) cells, termed "instruction," or whether cytokines act in a supportive role, termed "selection," whereby newly differentiating T(H) cells are given the proper signals for survival and proliferation. A recent paper by Mullen et al., which helps delineate the role of cytokines in T(H)1 cell development, is addressed by Nelson; it appears that cytokines act in the selection stage of T(H) cell maturation.