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Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples.
Am J Reprod Immunol 2011; 66 Suppl 1:44-56AJ

Abstract

PROBLEM

Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women.

METHOD OF STUDY

Distribution, location, cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from paired samples using immunohistochemistry, immunofluorescence, flow cytometry, and real-time quantitative RT-PCR.

RESULTS

The presence and in situ distribution of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+) Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In contrast, no statistically significant difference in numbers of circulating Treg cells between pregnant and non-pregnant women was found. The Foxp3(+) cells expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3, CD62L, and TGFβ1 mRNA consistent with Treg phenotype. The population of CD4(+) CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10-fold compared with PB in paired samples. Their cytokine expression was often similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-) cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naïve Treg cells.

CONCLUSION

(i) There is a local enrichment of Treg cells in decidua (ii) The exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an additional reservoir of Foxp3(+) naïve Treg cells that can be converted to 'classical' Treg cells in uterus.

Authors+Show Affiliations

Department of Clinical Microbiology/Clinical Immunology, Umeå University, Umeå, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21726337

Citation

Dimova, Tanya, et al. "Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25- Regulatory T-cell Populations Are Enriched in Human Early Normal Pregnancy Decidua: a Phenotypic Study of Paired Decidual and Peripheral Blood Samples." American Journal of Reproductive Immunology (New York, N.Y. : 1989), vol. 66 Suppl 1, 2011, pp. 44-56.
Dimova T, Nagaeva O, Stenqvist AC, et al. Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. Am J Reprod Immunol. 2011;66 Suppl 1:44-56.
Dimova, T., Nagaeva, O., Stenqvist, A. C., Hedlund, M., Kjellberg, L., Strand, M., ... Mincheva-Nilsson, L. (2011). Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. American Journal of Reproductive Immunology (New York, N.Y. : 1989), 66 Suppl 1, pp. 44-56. doi:10.1111/j.1600-0897.2011.01046.x.
Dimova T, et al. Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25- Regulatory T-cell Populations Are Enriched in Human Early Normal Pregnancy Decidua: a Phenotypic Study of Paired Decidual and Peripheral Blood Samples. Am J Reprod Immunol. 2011;66 Suppl 1:44-56. PubMed PMID: 21726337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. AU - Dimova,Tanya, AU - Nagaeva,Olga, AU - Stenqvist,Ann-Christin, AU - Hedlund,Malin, AU - Kjellberg,Lennart, AU - Strand,Magnus, AU - Dehlin,Eva, AU - Mincheva-Nilsson,Lucia, PY - 2011/7/6/entrez PY - 2011/7/8/pubmed PY - 2011/12/16/medline SP - 44 EP - 56 JF - American journal of reproductive immunology (New York, N.Y. : 1989) JO - Am. J. Reprod. Immunol. VL - 66 Suppl 1 N2 - PROBLEM: Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women. METHOD OF STUDY: Distribution, location, cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from paired samples using immunohistochemistry, immunofluorescence, flow cytometry, and real-time quantitative RT-PCR. RESULTS: The presence and in situ distribution of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+) Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In contrast, no statistically significant difference in numbers of circulating Treg cells between pregnant and non-pregnant women was found. The Foxp3(+) cells expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3, CD62L, and TGFβ1 mRNA consistent with Treg phenotype. The population of CD4(+) CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10-fold compared with PB in paired samples. Their cytokine expression was often similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-) cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naïve Treg cells. CONCLUSION: (i) There is a local enrichment of Treg cells in decidua (ii) The exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an additional reservoir of Foxp3(+) naïve Treg cells that can be converted to 'classical' Treg cells in uterus. SN - 1600-0897 UR - https://www.unboundmedicine.com/medline/citation/21726337/Maternal_Foxp3_expressing_CD4+_CD25+_and_CD4+_CD25__regulatory_T_cell_populations_are_enriched_in_human_early_normal_pregnancy_decidua:_a_phenotypic_study_of_paired_decidual_and_peripheral_blood_samples_ L2 - https://doi.org/10.1111/j.1600-0897.2011.01046.x DB - PRIME DP - Unbound Medicine ER -