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

C. S. Hsieh, A. B. Heimberger, J. S. Gold, A. O'Garra, K. M. Murphy

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Abstract

To address the mechanisms controlling T helper (T(h)) phenotype development, we used DO10, a transgenic mouse line that expresses the αβ 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 γ 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.

Original languageEnglish
Pages (from-to)6065-6069
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number13
DOIs
StatePublished - Jul 20 1992

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