IL-4 responsive CD4+ T cells specific for myelin basic protein:: IL-2 confers a prolonged postactivation refractory phase

This study compared myelin basic protein-specific T cells from Lewis rats that were derived in the presence of either rat IL-4 or IL-2. Interleukin-4 was a maintenance factor that enabled derivation of long-term T cell lines. When activated, IL-4 dependent lines were lacking in IL-2 production capacity but maintained high levels of responsiveness to IL-2 and recognized IL-2 as a dominant growth factor. Activated IL-4 dependent T cells rapidly reverted to a quiescent phenotype in the presence of IL-4 and rapidly regained myelin basic protein reactivity. In contrast, activated IL-2 dependent T cells that were propagated in IL-2 had a more persistent blastogenic phenotype and a prolonged refractory phase. Interleukin-4 dependent lines that were propagated in IL-2 up-regulated the capacity to produce IL-2 and also acquired prolonged postactivation refractoriness. Thus, IL-2 was a dominant growth factor that conferred prolonged activation-dependent non-responsiveness. The coupling of dominant growth factor activity with prolonged postactivation refractoriness may be associated with the requisite role of IL-2 in homeostatic self-tolerance.