DIFFERENTIAL REGULATION OF T-HELPER PHENOTYPE DEVELOPMENT BY INTERLEUKIN-4 AND INTERLEUKIN-10 IN AN ALPHA-BETA-T-CELL-RECEPTOR TRANSGENIC SYSTEM

To address the mechanisms controlling T helper (T(h)) phenotype development, we used DO10, a transgenic mouse line that expresses the alpha/beta-T-cell receptor from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting cells (APCs). We have examined the role of cytokines and APCs in the regulation of T(h) phenotype development. Interleukin 4 (IL-4) directs development toward the T(h2) phenotype, stimulating IL-4 and silencing IL-2 and interferon-gamma-production in developing T cells. Splenic APCs direct development toward the T(h1) phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody. The splenic APCs mediating these effects are probably macrophages or dendritic cells and not B cells, since IL-10 is incapable of affecting T(h) phenotype development when the B-cell hybridoma TA3 is used as the APC. These results suggest that early regulation of IL-4 and IL-10 in a developing immune response and the identity of the initiating APCs are critical in determining the T(h) phenotype of the developing T cells.