ABSTRACT
T lymphocytes play a central role in the immune response, both as effectors and as regulatory cells that modulate the function of numerous cell types, primarily those that participate in the body’s defense mechanisms. This regulatory function is provided either through direct cell-cell contact or via the secretion of various cytokines. Thus, the proper function of T cells is essential for the maintenance of normal homeostasis within and outside the immune system. Conversely, abnormalities in their function can lead to immunological diseases, e.g., autoimmunity or immunodeficiencies. The primary event leading to the activation and differentiation of mature T cells is the triggering of their antigen-specific T cell receptor (TCR) by its specific ligand which consists of a processed antigenic peptide presented in association with major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs) or appropriate target cells. This event triggers several signal transduction pathways that involve second messengers, protein kinases, phosphatases and other enzymes and key intermediates. This signaling cascade culminates with the induction of gene transcription according to defined genetic programs that are characteristic of the different T cell subsets, leading to the differentiation and proliferation of these cells. In addition, the proper development and selection of immature T cells in the thymus also depends on incompletely understood signaling events that dictate negative and positive selection processes and determine the specificity repertoire.
