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Lewis EL, Xu R, Beltra JC, et al. NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy. J Exp Med. 2021;219(1)doi: 10.1084/jem.20201599.
Lewis, E. L., Xu, R., Beltra, J. C., Ngiow, S. F., Cohen, J., Telange, R., Crane, A., Sawinski, D., Wherry, E. J., & Porrett, P. M. (2022). NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy. The Journal of experimental medicine, 219(1), . https://doi.org/10.1084/jem.20201599
Lewis, Emma L, et al. "NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy." The Journal of experimental medicine vol. 219,1 (2022). doi: https://doi.org/10.1084/jem.20201599
Lewis EL, Xu R, Beltra JC, Ngiow SF, Cohen J, Telange R, Crane A, Sawinski D, Wherry EJ, Porrett PM. NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy. J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20201599. Epub 2021 Dec 09. PMID: 34882194; PMCID: PMC8666877.
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J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20201599. Epub 2021 Dec 09.

NFAT-dependent and -independent exhaustion circuits program maternal CD8 T cell hypofunction in pregnancy.

The Journal of experimental medicine

Emma L Lewis, Rong Xu, Jean-Christophe Beltra, Shin Foong Ngiow, Jordana Cohen, Rahul Telange, Alexander Crane, Deirdre Sawinski, E John Wherry, Paige M Porrett

Affiliations

  1. Department of Obstetrics and Gynecology, The University of Pennsylvania, Philadelphia, PA.
  2. Department of Surgery, The University of Pennsylvania, Philadelphia, PA.
  3. Department of Systems Pharmacology and Translational Therapeutics, The University of Pennsylvania, Philadelphia, PA.
  4. Institute for Immunology, University of Pennsylvania, Philadelphia, PA.
  5. Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA.
  6. Department of Medicine, The University of Pennsylvania, Philadelphia, PA.
  7. Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL.
  8. Comprehensive Transplant Institute, The University of Alabama at Birmingham, Birmingham, AL.

PMID: 34882194 PMCID: PMC8666877 DOI: 10.1084/jem.20201599

Abstract

Pregnancy is a common immunization event, but the molecular mechanisms and immunological consequences provoked by pregnancy remain largely unknown. We used mouse models and human transplant registry data to reveal that pregnancy induced exhausted CD8 T cells (Preg-TEX), which associated with prolonged allograft survival. Maternal CD8 T cells shared features of exhaustion with CD8 T cells from cancer and chronic infection, including transcriptional down-regulation of ribosomal proteins and up-regulation of TOX and inhibitory receptors. Similar to other models of T cell exhaustion, NFAT-dependent elements of the exhaustion program were induced by fetal antigen in pregnancy, whereas NFAT-independent elements did not require fetal antigen. Despite using conserved molecular circuitry, Preg-TEX cells differed from TEX cells in chronic viral infection with respect to magnitude and dependency of T cell hypofunction on NFAT-independent signals. Altogether, these data reveal the molecular mechanisms and clinical consequences of maternal CD8 T cell hypofunction and identify pregnancy as a previously unappreciated context in which T cell exhaustion may occur.

© 2021 Lewis et al.

Conflict of interest statement

Disclosures: J. Cohen reported grants from National Institutes of Health outside the submitted work. E.J. Wherry is consulting or is an advisor for Merck, Marengo, Janssen, Related Sciences, Synthekin

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