Acquisition of Mature Functional Responsiveness in T Cells: Programming for Function via Signaling

Over fifteen years ago it was recognized that peripheral T lymphocytes are heterogeneous in their abilities to carry out particular functions. Distinct functional activities are associated with distinct cell-surface phenotypes. Thus, CD4^+ cells are greatly enriched for the ability to provide growth and differentiation factors for other T and B cells, whereas CD8^+ cells are correspondingly enriched for the ability to kill foreign or pathologically altered target cells. At the molecular level, we now understand that each of these functions reflects the transcriptional activation of particular sets of "response" genes, i.e., those encoding lymphokines and/or cytolytic molecules, when triggered by recognition of a foreign antigen. Thus, different T-cell subsets are defined by the fact that they respond to antigen by induction of different sets of genes. As all of these subsets are derived from common precursors, developing T cells must not only mature but also diverge in their properties in a regulated way. In this paper, we will consider how different programs of transcriptional inducibility become allocated to different sets of cells.