Transforming growth factor-beta (
TGF-beta), a product of neoplastic and hemopoietic cells, is a bifunctional regulator of the immune response. At femtomolar concentrations,
TGF-beta stimulates monocyte migration, and picomolar quantities induce synthesis of monocyte
growth factors, including
IL-1, that may promote tissue repair by regulating
fibrosis and angiogenesis. Paradoxically,
TGF-beta at picomolar concentrations also blocks the ability of
IL-1 to stimulate lymphocyte proliferation. At 0.01 to 1.0 ng/ml,
TGF-beta 1 and its homologue,
TGF-beta 2, suppress the IL-1-dependent murine thymocyte proliferation assay.
TGF-beta also inhibits human peripheral blood T lymphocyte mitogenesis. Inhibition of cell division appears to occur after activation of the lymphocytes inasmuch as neither gene expression nor translation of IL-2R is suppressed. Furthermore,
TGF-beta does not block synthesis of
IL-2. Therefore,
TGF-beta 1 and
TGF-beta 2 likely act at a site distal to
IL-1 to block lymphocyte
DNA synthesis. These findings suggest that
TGF-beta secreted in an inflammatory site may be beneficial in diminishing lymphocyte function while promoting
fibrosis and tissue repair. However,
TGF-beta generated by neoplastic tissues may provide a mechanism for unrestricted
tumor cell growth through its selective immunosuppressive effects.