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Prevention of T cell–driven complement activation and inflammation by tryptophan catabolism during pregnancy

Nature Immunology volume 2, pages 64–68 (2001)Cite this article

Abstract

Indoleamine 2,3 dioxygenase (IDO) activity during pregnancy protects developing fetuses from maternal immune responses in CBA mice. We show here that fetal allografts were rejected only in mating combinations where paternally inherited tissue antigens elicited potent maternal T cell responses after exposure to IDO inhibitor. IDO inhibitor treatment triggered extensive inflammation at the maternal-fetal interface in susceptible mating combinations, which was characterized by complement deposition and hemorrhagic necrosis. Identical inflammatory responses occurred in B cell–deficient (RAG-1−/−) mothers that carried a monoclonal cohort of CD8+ T cells specific for a single paternally inherited fetal major histocompatibility complex antigen. Thus, fetal allograft rejection was accompanied by a unique form of inflammation that was characterized by T cell–dependent, antibody-independent activation of complement. In contrast, no inflammation, complement deposition or T cell infiltration was elicited when mice carrying syngeneic fetuses were exposed to IDO inhibitor. These data show that IDO activity protects the fetus by suppressing T cell–driven local inflammatory responses to fetal alloantigens.

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Figure 1: Detection of C3 and Crry in decidua.
Figure 2: T cell infiltration and complement deposition at the maternal-fetal interface in B cell–deficient mice treated with IDO inhibitor.

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Acknowledgements

We thank D. McCool for technical assistance, A. Compton for administrative support and M. Litaker for statistical analysis. Supported by National Institutes of Health grants AI44219 to (A. L. M.), HL60137 (to D. H. M.) and AI40576 and AI44912 (to H. M.), the Medical College of Georgia Department of Medicine and the Carlos and Marguerite Mason Trust.

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Affiliations

  1. Department of Medicine, Program in Molecular Immunology, Institute of Molecular Medicine and Genetics, 1120 15 th St., Augusta, 30912, GA, USA

    Andrew L. Mellor, Jayabalan Sivakumar, Phillip Chandler & Kimberly Smith

  2. Pediatrics, Medical College of Georgia, 1120 15th St., Augusta, 30912, GA, USA

    David H. Munn

  3. Departments of Medicine and Pathology, Washington University School of Medicine, St. Louis, 63110, MO

    Hector Molina & Dailing Mao

  4. Veterans Administration Center, St. Louis, 63106, MO, USA

    Hector Molina & Dailing Mao

Authors
  1. Andrew L. Mellor
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  2. Jayabalan Sivakumar
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  3. Phillip Chandler
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  4. Kimberly Smith
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  5. Hector Molina
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  6. Dailing Mao
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  7. David H. Munn
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Correspondence to Andrew L. Mellor.

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Mellor, A., Sivakumar, J., Chandler, P. et al. Prevention of T cell–driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2, 64–68 (2001). https://doi.org/10.1038/83183

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