The role of endogenous lymphokines in T cell activation has been demonstrated. The proliferative response of type 2 T helper clones is inhibited by antibody specific for the lymphokine IL4, which is produced by these clones. This demonstrates that IL4 acts as an autocrine growth factor for these T cells. In addition, IL4 mRNA levels corresponding to a number of activation genes are inhibited by the presence of anti-IL4 antibody during T cell activation. In contrast, the level of mRNA is actually increased in the presence of this antibody, suggesting that an endogenously produced IL4 may normally down regulate its own gene transcription. The regulation of IL3, IL4, IL5, and GM-CSF lymphokine gene expression by type 2 helper clones was studied in more detail, using multiple inducing stimuli and pharmacologic inhibitors. It was found that independent (noncoordinate) regulation of discrete lymphokine genes can occur and is dependent upon the nature of the inducing stimulus. In particular, it was found that expression of IL4 and IL5 genes, but which are generally co-expressed by type 2 T helper clones in response to T cell receptor-mediated stimuli, can be independently regulated. The activation of T helper type 1 clone AE7.6 is influenced by the prior activation history of the cells. Sub-cloned T cells were carried in vivo either by stimulation with IL2 alone or by stimulation with specific antigen and antigen presenting cells in addition to IL2. Cell lines carried under both conditions were capable of proliferating in response to stimulation with anti-CD3 antibody. However, this stimulation induced strong phosphatidyl inositol hydrolysis and increased intracellular calcium concentrations only in cells which had been maintained by stimulation with IL2 alone; cells that had been repeatedly stimulated with specific antigen generated neither PI nor calcium responses to anti-CD3. The signaling pathways utilized by cloned T cells were therefore influenced by prior stimulation through the T cell receptor.
