The role of IFN-gamma in the production of Th2 subpopulations: implications for variable Th2-mediated pathologies in autoimmunity.
It has become increasingly apparent in studies of mutant mice and observations of disease that cytokine production by fully committed effector T cells within the Th1 and Th2 phenotype can vary within each group. This can potentially influence the type and effectiveness of a given immune response. The factors responsible for inducing variable Th1 and Th2 subtype responses have not been well established. Using transgenic mice expressing the myelin basic protein-specific TCR, we demonstrate here that two distinct populations of Th2 cells that are characterized primarily by differential IL-4 and IL-5 expression levels can be generated depending upon the levels of IFN-gamma present at the time of priming. We also demonstrate that populations expressing high levels of IL-4 relative to IL-5 vs those with intermediate levels of IL-4 relative to IL-5 are stable and possess distinct effector functions in an experimental autoimmune encephalomyelitis model.
Wensky
A
A
Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University Medical Center, New York, NY 10016, USA.
Marcondes
M C
MC
Lafaille
J J
JJ
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D018398:Homeodomain Proteins; D015848:Interleukin-5; D008222:Lymphokines; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D015847:Interleukin-4; D007371:Interferon-gamma