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Foxp3 regulates human natural CD4+CD25+ regulatory T-cell-mediated suppression of xenogeneic response.
Xenotransplantation. 2010 Mar-Apr; 17(2):121-30.X

Abstract

BACKGROUNDS

Cellular rejection of xenografts is predominantly mediated by CD4+ T cells. Foxp3 expressing human naturally occurring CD4+CD25+ regulatory T cells (nTregs) have been shown to suppress pathological and physiological immune responses, including the CD4+ T-cell-mediated anti-pig xenogeneic response in vitro. Although Foxp3 is required for nTreg development and their function, the precise role of Foxp3 in regulating Treg suppressive function in xenoimmune response remains to be identified.

METHODS

In vitro expanded human nTregs were transfected with fluorescein isothiocyanate -conjugated Foxp3 small interfering RNA (siRNA) by Lipofectamine 2000. Transfected nTregs were sorted by fluorescence-activated cell sorting, and then analyzed for Foxp3 gene and protein expression as well as their phenotypic characteristics. Human CD4+CD25- T cells were stimulated with xenogeneic pig peripheral blood mononuclear cell in the presence or absence of nTregs in a coculture or transwell system for evaluation of nTreg suppressive activity. The production of effector cytokines by xenoreactive CD4+CD25- T cells as well as suppressive cytokine by nTregs in their cocultures was examined by ELISA.

RESULTS

The siRNA-mediated Foxp3 knockdown resulted in impaired nTreg anergic state, downregulated expression of nTreg function associated molecules, and reduced production of suppressive cytokines by nTregs, which together leading to impaired nTreg-mediated suppression of CD4+CD25- T-cell proliferation and their effector cytokine production in response to xenogeneic stimulation.

CONCLUSIONS

This study demonstrates that Foxp3 expression is required for human nTregs to maintain their suppressive function in the xenoimmune response.

Authors+Show Affiliations

Center for Transplant and Renal Research, Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20522244

Citation

Sun, Lei, et al. "Foxp3 Regulates Human Natural CD4+CD25+ Regulatory T-cell-mediated Suppression of Xenogeneic Response." Xenotransplantation, vol. 17, no. 2, 2010, pp. 121-30.
Sun L, Yi S, O'Connell PJ. Foxp3 regulates human natural CD4+CD25+ regulatory T-cell-mediated suppression of xenogeneic response. Xenotransplantation. 2010;17(2):121-30.
Sun, L., Yi, S., & O'Connell, P. J. (2010). Foxp3 regulates human natural CD4+CD25+ regulatory T-cell-mediated suppression of xenogeneic response. Xenotransplantation, 17(2), 121-30. https://doi.org/10.1111/j.1399-3089.2010.00571.x
Sun L, Yi S, O'Connell PJ. Foxp3 Regulates Human Natural CD4+CD25+ Regulatory T-cell-mediated Suppression of Xenogeneic Response. Xenotransplantation. 2010 Mar-Apr;17(2):121-30. PubMed PMID: 20522244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Foxp3 regulates human natural CD4+CD25+ regulatory T-cell-mediated suppression of xenogeneic response. AU - Sun,Lei, AU - Yi,Shounan, AU - O'Connell,Philip J, PY - 2010/6/5/entrez PY - 2010/6/5/pubmed PY - 2010/9/15/medline SP - 121 EP - 30 JF - Xenotransplantation JO - Xenotransplantation VL - 17 IS - 2 N2 - BACKGROUNDS: Cellular rejection of xenografts is predominantly mediated by CD4+ T cells. Foxp3 expressing human naturally occurring CD4+CD25+ regulatory T cells (nTregs) have been shown to suppress pathological and physiological immune responses, including the CD4+ T-cell-mediated anti-pig xenogeneic response in vitro. Although Foxp3 is required for nTreg development and their function, the precise role of Foxp3 in regulating Treg suppressive function in xenoimmune response remains to be identified. METHODS: In vitro expanded human nTregs were transfected with fluorescein isothiocyanate -conjugated Foxp3 small interfering RNA (siRNA) by Lipofectamine 2000. Transfected nTregs were sorted by fluorescence-activated cell sorting, and then analyzed for Foxp3 gene and protein expression as well as their phenotypic characteristics. Human CD4+CD25- T cells were stimulated with xenogeneic pig peripheral blood mononuclear cell in the presence or absence of nTregs in a coculture or transwell system for evaluation of nTreg suppressive activity. The production of effector cytokines by xenoreactive CD4+CD25- T cells as well as suppressive cytokine by nTregs in their cocultures was examined by ELISA. RESULTS: The siRNA-mediated Foxp3 knockdown resulted in impaired nTreg anergic state, downregulated expression of nTreg function associated molecules, and reduced production of suppressive cytokines by nTregs, which together leading to impaired nTreg-mediated suppression of CD4+CD25- T-cell proliferation and their effector cytokine production in response to xenogeneic stimulation. CONCLUSIONS: This study demonstrates that Foxp3 expression is required for human nTregs to maintain their suppressive function in the xenoimmune response. SN - 1399-3089 UR - https://www.unboundmedicine.com/medline/citation/20522244/Foxp3_regulates_human_natural_CD4+CD25+_regulatory_T_cell_mediated_suppression_of_xenogeneic_response_ L2 - https://doi.org/10.1111/j.1399-3089.2010.00571.x DB - PRIME DP - Unbound Medicine ER -