The post-activation refractory phase: a mechanism to measure antigenic complexity and ensure self-tolerance among...

This paper outlines a model describing how the post-activation refractory phase of mature T cells may promote adaptive self/nonself-discrimination among mature peripheral T cells in extrathymic tissues. This model is based on the following experimental observations. First, activation of myelin basic protein-specific T-helper cells elicits a single episode of interleukin 2 production followed by a 7-10 day refractory phase during which antigenic restimulation elicits proliferation but without interleukin 2 production or reexpression of encephalitogenic activity. Secondly, T lymphoblasts exhibiting post-activation refractoriness are substantially more susceptible to anergy as compared to resting T cells. Third, myelin basic protein-induced activation at low T-cell densities elicits a refractory phase that is prolonged as compared to that of high T-cell density cultures. These results support a model by which a pioneer T-cell encountering peripheral antigen produces a limited supply of interleukin 2. This T cell will upregulate effector functions or will become anergic, depending on continual immigration of additional antigen-reactive clones, each of which makes a limited supply of interleukin 2 before entering into the post-activation refractory phase. By this model, immune responses will be sustained in areas with high degrees of antigenic complexity (infectious process) but will falter in regions of low antigenic complexity (unaltered self tissues).