The ionic and biochemical basis for T-cell activation and proliferation. Potential causes of impaired T-cell function

The binding of mitogens to cells of different lineages triggers a series of ionic and biochemical events that are thought to be important for cell differentiation and growth. Lymphocytes share many of these pathways but may be deprived of others. Changes in cytosolic Ca2+ levels are pivotal in receptor-initiated signal transduction, especially for signaling IL2 gene transcription and IL2 synthesis/secretion. Antigen-presenting cells play a major role in triggering this Ca2+ response of T cells. The major component of the Ca2+ response appears to be transmembrane Ca2+ uptake, presumably through Ca2+ channels. Such ligand-gated Ca2+ channels are regulated differently from the Ca2+ channels of excitable cells. In addition to increases in Ca2+, there are other ion fluxes and biochemical events which are observed following ligand binding to specific receptors. Many of these events appear to be the consequence of cell activation but do not appear to be essential for the T-cell proliferative response. Further characterization of these pathways may explain the T-cell immunodeficiencies which appear in the presence of phenotypically normal T cells in the periphery.