Monocyte-dependent costimulatory effect of TGF- beta 1 on rat T-cell activation

TGF- beta 1 is known to have suppressive effects on both T-cell proliferation and effector functions, but costimulatory effects have also been reported. In the present investigation the effect of TGF- beta 1 is studied in vitro on T-cell proliferative responses of rat spleen cells and of lymph node cells to alloantigens (MLR), the superantigen Staphylococcal enterotoxin A (SEA) or IL-2. Without addition of TGF- beta 1, adherent, freshly isolated rat spleen monocytes have a suppressive effect on T-cell activation, which upon addition of TGF- beta 1 is reversed to a strong costimulatory effect. The costimulatory effect of TGF- beta 1 is shown to be entirely dependent on the presence of fresh monocytes. Costimulation is demonstrated when TGF- beta 1 is added to spleen cells at the start of the in vitro assays but not when added more than 24 h after the start. Costimulation is not demonstrable when TGF- beta 1 is added to lymph node cells alone but is readily detectable after admixture of freshly isolated spleen monocytes to the lymph node cells. TGF- beta 1 added at the end of culture induces suppression of T-cell activation irrespective of the presence or absence of monocytes. When TGF- beta 1 is added both at the start of an MLC and again after 4 days, the costimulatory effect is maintained, although somewhat moderated. The costimulatory effect of TGF- beta 1 is demonstrated as an increase of the T blast cell population of both CD4+ IL-2R+ and CD8+ IL-2R+ T-cell subsets, whereas the suppressive effect of TGF-beta 1 is shown as reduction of the same parameters.