Autoregulation Of T-Cell Proliferation

Abstract

One of the unique characteristics of the immune system is the exquisite specificity of reactivity. The introduction of an antigen, either in vivo or in vitro, results in a clone-specific proliferative expansion and differentiation to effector function. Of course, this specificity of reactivity resides in the clonal distribution of antigen receptors on B cells and T cells; each cell reacts with high affinity only to one antigen epitope. As such, this phenomenon precludes the expression of interleukin 2 (IL-2) receptors by lymphocytes that have yet to encounter their specific antigen, since multiple clonal antigen specificities would react if non-antigen-specific cells were also capable of responding to IL-2. In practice, IL-2 receptors can not be detected on freshly isolated lymphocytes¹. Moreover, immunoaffinity-purified, homogeneous IL-2 does not generate a proliferative response provided potential antigens are excluded from the culture system². Accordingly, one of the unique aspects of the IL-2 hormone-receptor system is the inducibility of IL-2 receptors³: the immune system remains quiescent until environmental, foreign material is introduced, whereupon the IL-2 hormone-receptor system functions to transfer these environmental molecular signals to an internal, endocrine-like control mechanism. Consequently, the rapidity of induction, magnitude, and duration of T-cell proliferative responses are dictated by the rate and extent of IL-2 and IL-2 receptor gene expression^3,4.