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Is there a role for HLA‐G in the induction of regulatory T cells during the maintenance of a healthy pregnancy?
Author(s) -
AlKhunaizi Nada R.,
Tabbara Khaled S.,
Farid Eman M.
Publication year - 2020
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13259
Subject(s) - foxp3 , hla g , il 2 receptor , pregnancy , human leukocyte antigen , medicine , andrology , immune system , fetus , immunology , downregulation and upregulation , biology , antigen , t cell , genetics , gene
Problem Pregnancy remains an immune challenge for the uterus that has to adapt to a semi‐allogeneic fetus using various regulatory mechanisms. Both HLA‐G and regulatory T cells (CD4 + CD25 + FOXP3 + T regs ) are upregulated in successful pregnancy, but not in abortion. It is unclear if HLA‐G plays a role in the upregulation of regulatory cells. Method of Study We measured the level of both sHLA‐G and T reg cells in the blood of healthy pregnant multigravida, unexplained recurrent spontaneous abortions (URSA) and healthy non‐pregnant and nulliparous females. We cultured peripheral blood lymphocytes of healthy non‐pregnant multigravida females who never had an abortion with lymphocytes of their partners at ratio of 1:1, with and without sHLA‐G to detect changes in number of T reg cells, or relevant cytokines. Results Soluble HLA‐G concentrations and T reg cells percentage were significantly lower in women with URSA as compared to healthy pregnant multigravida women and were comparable to healthy non‐pregnant nulliparous women. Percentage of T regs increased between zero time and mixed lymphocyte cultures (MLC) in both cultures with and without recombinant sHLA‐G but no significant difference between the two cultures. When stimulated with sHLA‐G the mean extracellular IL‐10 concentration was unchanged, while the mean INF‐γ concentration was slightly higher with no significant difference. Intracellular TGF‐β was higher in CD4 + cells after incubation with sHLA‐G. Conclusion The results of this study are consistent with previous studies on the role of sHLA‐G and T reg cells in inducing immune‐tolerance in pregnancy. The results also suggest a possible role for HLA‐G in the enrichment of T reg cells.