T cell activation is a key event triggering an antigen specific immune response of the organism. The process is induced primarily by signal generated by direct interaction of T cell receptor (TCR) with antigen bound to major histocompatibile complex (MHC) on antigen presenting cell (APC). Although the signal is critical to excite immune response, however additional, costimulating signal is required. The major second signal is generated by interaction of CD28 molecule expressed on most T lymphocytes with its natural ligands CD80 and CD86 located on APCs. Signal excited by CD28 triggering involves multiple second messenger cascades, leading to activation of transcription factors and finally results in cell proliferation, cytokine production, and generation of effector function. The importance of CD28-delivered costimulatory signals was proven in experiments with CD28-deficient mice. T cells from these mice exhibit, impaired pattern of cytokine secretion, defects in T cell dependent antibody production. Certain forms of immunopathology might result from the aberrant regulation of CD28 expression.