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

• Published in: Immunology and cell biology 2003-02, Vol.81 (1), p.8-19
• Main Authors: Mannie, Mark D, Fraser, Dana J, McConnell, Thomas J
• Format: Article
• Language: English
• Subjects: Animals; antigen presentation; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; experimental autoimmune encephalomyelitis; Interleukin-2 - metabolism; Interleukin-4 - metabolism; major histocompatibility complex; multiple sclerosis; Myelin Basic Protein - immunology; Rats; Rats, Inbred Lew; T cell receptors; T cells; Th2 Cells
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1046/j.1440-1711.2003.01131.x

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.