It is now apparent that the
transforming growth factor beta (
TGF-beta) family of
proteins has potent immunoregulatory properties ranging from effects on the growth and differentiation of primitive stem cells to the differentiated functions of immune effector cells. Although most reports have described the immunosuppressive activities of
TGF-beta, recent evidence supports the concept that
TGF-beta can have both inhibitory and stimulatory actions on these systems. Recently, it has been found that
TGF-beta can have autocrine as well as paracrine effects on the immune system, indicating that immune cells can activate the inactive secreted form of
TGF-beta. Furthermore,
TGF-beta has differential intracellular effects on
cell surface receptor modulation,
tyrosine phosphorylation, and
cytokine gene transcription as well as cell-mediated cytotoxicity. Importantly, the administration of
TGF-beta has proven beneficial in several
animal disease models such as
septic shock, allograft rejection, and autoimmunity. Moreover, the increased levels of
TGF-beta found in several disease states associated with immunosuppression such as different forms of
malignancy, chronic degenerative diseases, and
AIDS implicate the involvement of
TGF-beta in the pathogenesis of some diseases. Ultimately, well designed clinical trials will determine whether the exciting potential of
TGF-beta can be used to treat or prevent disease.