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 prolife ration and effector functions,but costimulatory effects have also been reported. In the present investigation the effect of TGF-beta 1 is st udied in vitro on T-cell proliferative responses of rat spleen cells a nd of lymph node cells to alloantigens (MLR), the superantigen Staphyl ococcal enterotoxin A (SEA) or IL-2. Without addition of TGF-beta 1, a dherent, freshly isolated rat spleen monocytes have a suppressive effe ct on T-cell activation, which upon addition of TGF-beta 1 is reversed to a strong costimulatory effect. The costimulatory effect of TGF-bet a 1 is shown to be entirely dependent on the presence of fresh monocyt es. Costimulation is demonstrated when TGF-beta 1 is added to spleen c ells 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 a dmixture 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.