THE 3 ISOFORMS OF TRANSFORMING-GROWTH-FACTOR-BETA CO-STIMULATE RAT T-CELLS AND INHIBIT LYMPHOCYTE APOPTOSIS

In this study the three different mammalian isoforms of transforming g rowth factor-beta (TGF-beta) were compared with regard to their effect on the response of rat T lymphocytes to the superantigen, staphylococ cal enterotoxin A (SEA), All different isozymes were found to increase the proliferative response of rat T lymphocytes, which was accompanie d by a significantly lower percentage of apoptotic cells than prolifer ation in the absence of TGF-beta. The same effect of TGF-beta was obse rved on the generation of apoptotic cells in an allo response (mixed l ymphocyte reaction). TGF-beta(2) and TGF-beta(3) were three to 10-fold more potent than TGF-beta(1) as co-stimulators of T lymphocytes, and equal in decreasing the percentage of apoptotic T cells. TGF-beta(1) r educed the frequency and the number of cells undergoing apoptosis in T cells and, to an even higher degree, among B lymphocytes. TGF-beta di d not seem to affect the production of the apoptosis inducer, tumour n ecrosis factor-alpha (TNF-alpha), neither at the mRNA level nor at the protein level. Neutralizing antibodies against the cytokine, TNF-alph a, decreased the percentage of apoptotic cells among T cells respondin g to SEA, both in the absence and in the presence of added TGF-beta(1) . Thus, when TGF-beta acts as a co-stimulator for T-cell activation it inhibits the induction of apoptosis and sustains the number of viable cells.