UNCOUPLING IL-2 PRODUCTION FROM APOPTOSIS AND TNF PRODUCTION BY CHANGING THE SIGNAL THROUGH THE TCR

T cells may discriminate between stimuli in a variety of ways, includi ng the presence of cytokines or other costimulatory signals, the type of Ag (peptide, superantigen, or allorecognition), or the magnitude of the signal through the TCR, We have used anti-CD3 stimulation of T hy bridomas to examine signals generated through the TCR in the absence o f exogenous APCs, Soluble whole anti-CD3, but not F(ab')(2) anti-CD3, was able to stimulate the T hybridomas to produce IL-2. Plastic-bound anti-CD3, in contrast, stimulated TNF production, G(1) arrest, and apo ptosis by the T hybridoma. Engagement of the CD4 coreceptor on these c ells had no effect on the overall pattern of signaling observed, Altho ugh TNF production was correlated with apoptosis, anti-TNF treatment d id not prevent cell death or G(1) arrest, The response of the T hybrid oma to both forms of anti-CD3 included significant IL-2 production eve n at the lowest dose tested, However, soluble anti-CDS at the highest dose tested elicited only minor apoptosis, while plastic-bound anti-CD 3 elicited significant apoptosis even at the lowest dose, The differen ce in response was not evident at the level of phosphotyrosine protein s two min after cross-linking of the TCR.