EXPRESSION AND ROLE IN APOPTOSIS OF THE ALPHA-CHAINS AND BETA-CHAINS OF THE IFN-GAMMA RECEPTOR ON HUMAN TH1 AND TH2 CLONES

The mRNA and protein expression of the alpha- and beta-chains of IFN-g amma R were evaluated on a panel of human Th1 and Th2 clones. When cul tured in IL-2-conditioned medium, both types of clones expressed mRNA for the alpha- and beta-chains, and both chains were present in the cy toplasm. Membrane expression of the alpha-chain was higher on Th2 than on Th1, whereas the beta-chain was poorly expressed on both types but increased following IL-2 withdrawal or PHA stimulation. In addition, both types of clones overexpressed MHC class I glycoproteins following IFN-gamma R triggering by exogenous IFN-gamma, although the kinetics was slower in Th1, and this exposure induced mRNA for IRF-1. When thei r TCR was triggered in the absence of APC, Th1 only underwent apoptosi s. This activation-induced apoptosis was prevented by blocking of the alpha-chain or by IFN-gamma neutralization. Addition of IFN-gamma trig gered the apoptosis of Th2 clones. Apoptosis of both types of clones w as mediated by autocrine or exogenous IFN-gamma through the up-regulat ion of Fas-L expression, since anti-IFN-gamma R alpha mAb inhibited it s expression on Th1 and exogenous IFN-gamma increased its expression o n Th2. These results indicate that activated human Th1 and Th2 lymphoc ytes express IFN-gamma R alpha- and beta-chains and are both sensitive to signals provided by IFN-gamma. Data also suggest that IFN-gamma is critical for switching off their responses.