CD4plus T helper (The) subsets are characterized by their distinct cytokine production profiles. Th1 cells secrete IFNgamma, IL-2, and TNFbeta, while Th2 cells secrete IL-4,IL-5, IL-6, IL-10, and IL-13. The outcome of wide variety of immunologic processes including autoimmune, allergic, and infectious diseases has been demonstrated to be dependent on the development of the appropriate Th1 or Th2 subset. The molecular basis for the restricted expression of cytokine genes in the T helper subsets has remained elusive. Dr. Glimcher's laboratory has recently determined that the c-maf transcription factor is expressed only by Th2 cells and not Th1 cells. Moreover, c-maf appears to be a critical component for transcription of the Th2 specific cytokine gene IL-4. Thus c-maf may be and essential regulatory factor in Th2 development. The priority of this project is to address c-maf's role in The phenotype development in vitro and in vivo by generating transgenic mice with the c-mac gene targeted to the T cell lineage. In addition, this project will examine the molecular basis of c-maf's Th2 restricted expression. The proposed analysis of the in vitro and in vivo regulation of c-maf will determine the role this factor plays in The phenotype development. An understanding of the molecular mechanisms regulating The specific cytokine expression is essential for our understanding of this critical regulatory point of the immune response.
