The role of IFN-gamma in the production of Th2 subpopulations: implications for variable Th2-mediated pathologies in

A Wensky1, M C Marcondes, J J Lafaille

  • 1Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University Medical Center, New York, NY 10016, USA.

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.

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