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CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.

Publication ,  Journal Article
Halkias, J; Rackaityte, E; Hillman, SL; Aran, D; Mendoza, VF; Marshall, LR; MacKenzie, TC; Burt, TD
Published in: J Clin Invest
May 30, 2019

BACKGROUND: While the human fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown. METHODS: We analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with pro-inflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared to healthy term controls. RESULTS: We identified a transcriptionally distinct population of CD4+ T cells characterized by expression of the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF). PLZF+ CD4+ T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced pro-inflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFNγ in a fetal-specific manner. IFNγ-producing PLZF+ CD4+ T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation. CONCLUSION: Our work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 30, 2019

Volume

129

Issue

9

Start / End Page

3562 / 3577

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Promyelocytic Leukemia Zinc Finger Protein
  • Pregnancy
  • Phenotype
  • NK Cell Lectin-Like Receptor Subfamily B
  • Mucous Membrane
  • Lymphoid Tissue
  • Lymphocyte Activation
  • Leukocytes, Mononuclear
  • Intestines
 

Citation

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Halkias, J., Rackaityte, E., Hillman, S. L., Aran, D., Mendoza, V. F., Marshall, L. R., … Burt, T. D. (2019). CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells. J Clin Invest, 129(9), 3562–3577. https://doi.org/10.1172/JCI125957
Halkias, Joanna, Elze Rackaityte, Sara L. Hillman, Dvir Aran, Ventura F. Mendoza, Lucy R. Marshall, Tippi C. MacKenzie, and Trevor D. Burt. “CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.J Clin Invest 129, no. 9 (May 30, 2019): 3562–77. https://doi.org/10.1172/JCI125957.
Halkias J, Rackaityte E, Hillman SL, Aran D, Mendoza VF, Marshall LR, et al. CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells. J Clin Invest. 2019 May 30;129(9):3562–77.
Halkias, Joanna, et al. “CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.J Clin Invest, vol. 129, no. 9, May 2019, pp. 3562–77. Pubmed, doi:10.1172/JCI125957.
Halkias J, Rackaityte E, Hillman SL, Aran D, Mendoza VF, Marshall LR, MacKenzie TC, Burt TD. CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells. J Clin Invest. 2019 May 30;129(9):3562–3577.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 30, 2019

Volume

129

Issue

9

Start / End Page

3562 / 3577

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Promyelocytic Leukemia Zinc Finger Protein
  • Pregnancy
  • Phenotype
  • NK Cell Lectin-Like Receptor Subfamily B
  • Mucous Membrane
  • Lymphoid Tissue
  • Lymphocyte Activation
  • Leukocytes, Mononuclear
  • Intestines