CD161 contributes to prenatal immune suppression of IFNγ-producing PLZF+ T cells.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Halkias, J; Rackaityte, E; Hillman, SL; Aran, D; Mendoza, VF; Marshall, LR; MacKenzie, TC; Burt, TD
Published Date
- May 30, 2019
Published In
Volume / Issue
- 129 / 9
Start / End Page
- 3562 - 3577
PubMed ID
- 31145102
Pubmed Central ID
- PMC6715406
Electronic International Standard Serial Number (EISSN)
- 1558-8238
Digital Object Identifier (DOI)
- 10.1172/JCI125957
Language
- eng
Conference Location
- United States