Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system.

作者：Chyi‐Song Hsieh, Amy B. Heimberger, Jennifer S. Gold, Anne O’Garra, KENNETH M. M. MURPHY · 发表于：Proceedings of the National Academy of Sciences · 年份：1992 · DOI：10.1073/pnas.89.13.6065 · 被引用次数：753 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

To address the mechanisms controlling T helper (Th) 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 Th phenotype development. Interleukin 4 (IL-4) directs development toward the Th2 phenotype, stimulating IL-4 and silencing IL-2 and interferon gamma production in developing T cells. Splenic APCs direct development toward the Th1 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 Th 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 Th phenotype of the developing T cells.