Transforming growth factor-beta 1 enhances the generation of allospecific cytotoxic T lymphocytes.

We investigated the effects of transforming growth factor-beta 1 (TGF-beta 1) on the proliferation and generation of murine T lymphocytes in vitro. TGF-beta 1 suppressed T- and B-lymphocyte proliferation, mixed lymphocyte reaction (MLR), and the generation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells. On the other hand, TGF-beta 1 significantly enhanced the generation of allospecific cytotoxic T lymphocytes (CTL) at low concentrations (0.01-1 ng/ml) in a dose-dependent manner and restored it to the control level at higher concentrations (10-40 ng/ml). Allospecific CTL generation by TGF-beta 1 was maximally enhanced when added at the beginning of culture. Less enhancement occurred when the addition was delayed. Anti-TGF-beta 1 antibody completely abolished the enhancing effects of TGF-beta 1. Furthermore, platelet-derived TGF-beta (pTGF-beta) as well as recombinant TGF-beta 1 similarly enhanced the generation of allospecific CTL. These data demonstrate that TGF-beta has not only immunosuppressive effects but also immuno-enhancing effects in vitro.