The functional repertoire of activated T lymphocytes is in large part mediated by lymphokine secretion following T cell activation via one of several transmembrane receptors including TCR/CD3 and CD2. While activation via the TCR/CD3 pathway is the basis for antigen specific T cell responses, CD2 mediated activation underlies antigen independent proliferation, including autoimmune T cell activation. In particular, hematopoietic progenitor cell proliferation can be directly regulated by autoregulatory CD2 activated T cells. Generation of a regulatory (suppressive) T lymphocyte subset occurs when normal cycling HLA-- DR+CD58+progenitor cells induce proliferation of autologous CD4+CD2+T cells. Activation of T cells via the CD2 pathway also appears to generate suppressive T cell lymphokines, specifically tumor necrosis factor-alpha (TNFalpha) and to a lesser extent interferon-gamma (INFgamma). Thus study of the CD2 pathway of T cell activation is of paramount importance in understanding regulation of hematopoiesis. To study the hypothesis that suppressive lymphokines regulate stem cell proliferation, the colony stimulating factors (CSFs) and cytokines produced by CD2 activated, and by auto-activated T cells will be identified. Additionally, the T cell subsets which secrete lymphokines in response to alpha/CD2 stimulation will be identified. If preferential gene transcription of specific suppressive cytokines, e.g. TNFAlpha is confirmed, then the T cell specific molecular mechanisms regulating the transcription of the TNFAlpha gene will be characterized. This research is important in expanding our understanding of autoregulatory hematopoietic homeostasis, receptor-specific T cell activation, and in characterizing bone marrow transplant engraftment.
