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Direct and Indirect Inhibition of Th1 Development by Progesterone and Glucocorticoids

Hideki Miyaura and Makoto Iwata
J Immunol February 1, 2002, 168 (3) 1087-1094; DOI: https://doi.org/10.4049/jimmunol.168.3.1087
Hideki Miyaura
*Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan; and
†Chemicals Assessment Center, Chemicals Evaluation and Research Institute, Fukuoka, Japan
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Makoto Iwata
*Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan; and
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Abstract

Progesterone may contribute to the maternal suppression of immunity to the fetus by modulating the Th1/Th2 balance. To clarify whether progesterone directly or indirectly affects T cell differentiation, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two pulse stimulations with defined combinations of ionomycin and PMA followed by the treatment with IL-12, IL-4, and IL-2. In the second system, functional differentiation was induced in purified naive CD4 T cells with cytokines and Abs to CD3 and CD28. In both systems, progesterone added with cytokines suppressed Th1 development at concentrations associated with pregnancy, but enhanced the development of IL-10-producing Th2 cells. Because IL-10 is known to inhibit APC production of IL-12, Th1 development may be also suppressed indirectly by progesterone. However, progesterone failed to enhance IL-10 production in the absence of IL-12. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 inhibited Th1 development and enhanced Th2 development, as did progesterone, indicating that p38 MAPK and extracellular signal-regulated kinase pathways are involved in Th1 development. However, the progesterone effects may not be simply due to a modulation of MAPK activities, because the inhibitor did not significantly affect the development of IL-10-producing cells in the presence or absence of progesterone. Glucocorticoids exerted effects similar to those of progesterone on Th1/Th2 development even at lower concentrations. These results suggest that progesterone as well as glucocorticoids directly inhibit Th1 development and enhance Th2 development.

  • Received July 26, 2001.
  • Accepted November 16, 2001.
  • Copyright © 2002 by The American Association of Immunologists
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The Journal of Immunology: 168 (3)
The Journal of Immunology
Vol. 168, Issue 3
1 Feb 2002
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Direct and Indirect Inhibition of Th1 Development by Progesterone and Glucocorticoids
Hideki Miyaura, Makoto Iwata
The Journal of Immunology February 1, 2002, 168 (3) 1087-1094; DOI: 10.4049/jimmunol.168.3.1087

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Direct and Indirect Inhibition of Th1 Development by Progesterone and Glucocorticoids
Hideki Miyaura, Makoto Iwata
The Journal of Immunology February 1, 2002, 168 (3) 1087-1094; DOI: 10.4049/jimmunol.168.3.1087
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