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Increased CD4+CD25+Foxp3+ regulatory T cells in tolerance induced by portal venous injection.
Surgery 2009; 145(6):663-74S

Abstract

BACKGROUND

A portal vein injection (PVI) of allogeneic donor antigen is known to prolong the survival of a subsequently transplanted allograft; however, the underlying mechanism remains to be clarified.

METHODS

Irradiated C57BL/6 (B6) splenocytes were injected into BALB/c mice via the portal vein. Seven days after injection, the proportions of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells were determined in the blood, liver, and spleen. CD4(+) and CD8(+) T cells were isolated from BALB/c mice that received PVI of B6 splenocytes (PVI mice), adoptively transferred into recipient BALB/c mice 1 day before B6 or third-party C3H heart transplantation, and graft survival was compared. B6 or C3H heart allografts were implanted into anti-CD25 monoclonal antibody (mAb)-treated PVI and untreated PVI mice, and graft survivals were compared. The percentages of CD4(+)CD25(+)Foxp3(+) Treg, cytokine profiles, and ratios of apoptosis were determined in anti-CD25 mAb-treated PVI and untreated PVI mice.

RESULTS

PVI of allogeneic cells induced antigen-specific tolerance and increased the percentage of CD4(+)CD25(+)Foxp3(+) Treg. Adoptive transfer of CD4(+) T cells, but not CD8(+) T cells, from PVI mice prolonged B6 heart allograft survival. Depletion of CD4(+)CD25(+) T cells prevented the induction of tolerance and decreased the percentage of CD4(+)CD25(+)Foxp3(+) Treg in the CD3(+) T-cell pool, and thus was associated with decreased production of interleukin (IL)-4 and apoptosis of T cells.

CONCLUSION

Increased CD4(+)CD25(+)Foxp3(+) Treg play an important role in portal vein tolerance induction, at least partly via increasing the production of IL-4 and decreasing apoptosis of T cells.

Authors+Show Affiliations

Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.No 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

19486771

Citation

He, Fan, et al. "Increased CD4+CD25+Foxp3+ Regulatory T Cells in Tolerance Induced By Portal Venous Injection." Surgery, vol. 145, no. 6, 2009, pp. 663-74.
He F, Chen Z, Xu S, et al. Increased CD4+CD25+Foxp3+ regulatory T cells in tolerance induced by portal venous injection. Surgery. 2009;145(6):663-74.
He, F., Chen, Z., Xu, S., Cai, M., Wu, M., Li, H., & Chen, X. (2009). Increased CD4+CD25+Foxp3+ regulatory T cells in tolerance induced by portal venous injection. Surgery, 145(6), pp. 663-74. doi:10.1016/j.surg.2009.01.016.
He F, et al. Increased CD4+CD25+Foxp3+ Regulatory T Cells in Tolerance Induced By Portal Venous Injection. Surgery. 2009;145(6):663-74. PubMed PMID: 19486771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased CD4+CD25+Foxp3+ regulatory T cells in tolerance induced by portal venous injection. AU - He,Fan, AU - Chen,Zhishui, AU - Xu,Shengyuan, AU - Cai,Ming, AU - Wu,Min, AU - Li,Hongzhou, AU - Chen,Xiaoping, Y1 - 2009/04/19/ PY - 2008/09/01/received PY - 2009/01/15/accepted PY - 2009/6/3/entrez PY - 2009/6/3/pubmed PY - 2009/7/9/medline SP - 663 EP - 74 JF - Surgery JO - Surgery VL - 145 IS - 6 N2 - BACKGROUND: A portal vein injection (PVI) of allogeneic donor antigen is known to prolong the survival of a subsequently transplanted allograft; however, the underlying mechanism remains to be clarified. METHODS: Irradiated C57BL/6 (B6) splenocytes were injected into BALB/c mice via the portal vein. Seven days after injection, the proportions of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells were determined in the blood, liver, and spleen. CD4(+) and CD8(+) T cells were isolated from BALB/c mice that received PVI of B6 splenocytes (PVI mice), adoptively transferred into recipient BALB/c mice 1 day before B6 or third-party C3H heart transplantation, and graft survival was compared. B6 or C3H heart allografts were implanted into anti-CD25 monoclonal antibody (mAb)-treated PVI and untreated PVI mice, and graft survivals were compared. The percentages of CD4(+)CD25(+)Foxp3(+) Treg, cytokine profiles, and ratios of apoptosis were determined in anti-CD25 mAb-treated PVI and untreated PVI mice. RESULTS: PVI of allogeneic cells induced antigen-specific tolerance and increased the percentage of CD4(+)CD25(+)Foxp3(+) Treg. Adoptive transfer of CD4(+) T cells, but not CD8(+) T cells, from PVI mice prolonged B6 heart allograft survival. Depletion of CD4(+)CD25(+) T cells prevented the induction of tolerance and decreased the percentage of CD4(+)CD25(+)Foxp3(+) Treg in the CD3(+) T-cell pool, and thus was associated with decreased production of interleukin (IL)-4 and apoptosis of T cells. CONCLUSION: Increased CD4(+)CD25(+)Foxp3(+) Treg play an important role in portal vein tolerance induction, at least partly via increasing the production of IL-4 and decreasing apoptosis of T cells. SN - 1532-7361 UR - https://www.unboundmedicine.com/medline/citation/19486771/Increased_CD4+CD25+Foxp3+_regulatory_T_cells_in_tolerance_induced_by_portal_venous_injection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-6060(09)00086-5 DB - PRIME DP - Unbound Medicine ER -