Th1 or th2: How an appropriate T helper response can be made

Two types of T helper (Th) cells have been defined on the basis of their cytokine secretion patterns. The decision of a naive T cell to differentiate into Th1 or Th2 is crucial, since to a first approximation it determines whether a cell-mediated or humoral immune response is triggered against a particular pathogen, which profoundly influences disease outcome. Here we show that the internal behaviour of the T helper system, which emerges from regulatory mechanisms 'built into' the T helper system, itself can usually select the appropriate T helper response. This phenomenon arises from an initial Th1 bias together with the induction of Th1 --> Th2 switches when Th1 effecters do not. lead to efficient antigen clearance. The occurrence of these shifts is based on the antigen dose dependence of T helper differentiation, which is a consequence of asymmetries in cross-suppression, Critical for this feature is the late with which Th2 cells undergo antigen-induced cell death. (C) 2001 Society for Mathematical Biology.