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

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  • 1. Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
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    • Hsieh CS 1
    (1 author)

Proceedings of the National Academy of Sciences of the United States of America, 01 Jul 1992, 89(13):6065-6069
https://doi.org/10.1073/pnas.89.13.6065 PMID: 1385868 PMCID: PMC49438

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Abstract 

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.

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Proc Natl Acad Sci U S A. 1992 Jul 1; 89(13): 6065–6069.
PMCID: PMC49438
PMID: 1385868

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

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

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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