IL‐4 responsive CD4 + T cells specific for myelin basic protein: IL‐2 confers a prolonged postactivation refractory phase
- 1 February 2003
- journal article
- research article
- Published by Wiley in Immunology & Cell Biology
- Vol. 81 (1) , 8-19
- https://doi.org/10.1046/j.1440-1711.2003.01131.x
Abstract
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.Keywords
Funding Information
- National Multiple Sclerosis Society
This publication has 46 references indexed in Scilit:
- THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic FunctionsAnnual Review of Immunology, 1999
- Regulation of Interleukin (IL)-12 Receptor β2 Subunit Expression by Endogenous IL-12: A Critical Step in the Differentiation of Pathogenic Autoreactive T CellsThe Journal of Experimental Medicine, 1999
- Partial Agonism Elicits an Enduring Phase of T-Cell-Mediated Antigen PresentationCellular Immunology, 1998
- The Structure and Function of γс-Dependent Cytokines and Receptors: Regulation of T Lymphocyte Development and HomeostasisCritical Reviews in Immunology, 1998
- Myelin Basic Protein–specific T Helper 2 (Th2) Cells Cause Experimental Autoimmune Encephalomyelitis in Immunodeficient Hosts Rather than Protect Them from the DiseaseThe Journal of Experimental Medicine, 1997
- Interleukin-2 Is Indispensable for Development of Immunological Self-ToleranceClinical Immunology and Immunopathology, 1996
- IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune diseaseImmunology Today, 1996
- Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin‐2‐deficient colitisEuropean Journal of Immunology, 1995
- Disruption of the murine IL-4 gene blocks Th2 cytokine responsesNature, 1993
- Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cellsEuropean Journal of Immunology, 1991