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In vitro-expanded CD4(+)CD25(high)Foxp3(+) regulatory T cells controls corneal allograft rejection.
Hum Immunol 2012; 73(11):1061-7HI

Abstract

AIMS

Natural CD4(+)CD25(+) regulatory cells (nTregs) have been implicated in maintaining peripheral immune tolerance. This study aims to test whether immunotherapy using in vitro-expanded Treg (iTregs) could suppress allograft rejection in corneal transplantation model.

METHODS

Natural CD4(+)CD25(+) T cells were freshly purified from naïve mice and expanded in vitro by culturing with anti-CD3/CD28-coated Dynabeads, interleukin (IL)-2 and transforming growth factor (TGF-β1). Suppression ability of iTregs was assayed by co-culturing with CD4(+)CD25(-) T cells (Teff) in vitro and by targeting corneal allograft rejection in vivo. Tracking of iTreg after adoptive transfer in vivo were examined by CFSE labeling.

RESULTS

Natural Treg cells were expanded by culturing with anti-CD3/CD28-coated Dynabeads in the presence of IL-2 and TGF-β1. Compared with nTregs, iTregs had similar expression of CD62L, and PD- L1, lower expression of CD69, higher levels of PD-1, CD25, and Foxp3. iTreg cells exerted stronger suppression function than natural Treg cells when cocultured with CD4(+)CD25(-) T cells in vitro and prevented fully MHC-mismatched corneal allograft rejection. Survival of iTreg cells could suppress alloimmune reaction and most prone to migrate to graft draining LNs and spleens. Moreover, maintaining CD25 expression on iTregs was indicative for preservation of allosuppression.

CONCLUSION

Therapeutic use of in vitro-expanded CD4(+)CD25(+) T cells may be a effective and safe tool for controlling allograft rejection and may help induce allograft tolerance.

Authors+Show Affiliations

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmic and Visual Science Key Lab, Beijing, 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

Language

eng

PubMed ID

22939904

Citation

Guo, Xuming, et al. "In Vitro-expanded CD4(+)CD25(high)Foxp3(+) Regulatory T Cells Controls Corneal Allograft Rejection." Human Immunology, vol. 73, no. 11, 2012, pp. 1061-7.
Guo X, Jie Y, Ren D, et al. In vitro-expanded CD4(+)CD25(high)Foxp3(+) regulatory T cells controls corneal allograft rejection. Hum Immunol. 2012;73(11):1061-7.
Guo, X., Jie, Y., Ren, D., Zeng, H., Zhang, Y., He, Y., & Pan, Z. (2012). In vitro-expanded CD4(+)CD25(high)Foxp3(+) regulatory T cells controls corneal allograft rejection. Human Immunology, 73(11), pp. 1061-7. doi:10.1016/j.humimm.2012.08.014.
Guo X, et al. In Vitro-expanded CD4(+)CD25(high)Foxp3(+) Regulatory T Cells Controls Corneal Allograft Rejection. Hum Immunol. 2012;73(11):1061-7. PubMed PMID: 22939904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro-expanded CD4(+)CD25(high)Foxp3(+) regulatory T cells controls corneal allograft rejection. AU - Guo,Xuming, AU - Jie,Ying, AU - Ren,Dong, AU - Zeng,Hui, AU - Zhang,Yingnan, AU - He,Yan, AU - Pan,Zhiqiang, Y1 - 2012/08/29/ PY - 2012/03/05/received PY - 2012/08/14/revised PY - 2012/08/22/accepted PY - 2012/9/4/entrez PY - 2012/9/4/pubmed PY - 2013/5/10/medline SP - 1061 EP - 7 JF - Human immunology JO - Hum. Immunol. VL - 73 IS - 11 N2 - AIMS: Natural CD4(+)CD25(+) regulatory cells (nTregs) have been implicated in maintaining peripheral immune tolerance. This study aims to test whether immunotherapy using in vitro-expanded Treg (iTregs) could suppress allograft rejection in corneal transplantation model. METHODS: Natural CD4(+)CD25(+) T cells were freshly purified from naïve mice and expanded in vitro by culturing with anti-CD3/CD28-coated Dynabeads, interleukin (IL)-2 and transforming growth factor (TGF-β1). Suppression ability of iTregs was assayed by co-culturing with CD4(+)CD25(-) T cells (Teff) in vitro and by targeting corneal allograft rejection in vivo. Tracking of iTreg after adoptive transfer in vivo were examined by CFSE labeling. RESULTS: Natural Treg cells were expanded by culturing with anti-CD3/CD28-coated Dynabeads in the presence of IL-2 and TGF-β1. Compared with nTregs, iTregs had similar expression of CD62L, and PD- L1, lower expression of CD69, higher levels of PD-1, CD25, and Foxp3. iTreg cells exerted stronger suppression function than natural Treg cells when cocultured with CD4(+)CD25(-) T cells in vitro and prevented fully MHC-mismatched corneal allograft rejection. Survival of iTreg cells could suppress alloimmune reaction and most prone to migrate to graft draining LNs and spleens. Moreover, maintaining CD25 expression on iTregs was indicative for preservation of allosuppression. CONCLUSION: Therapeutic use of in vitro-expanded CD4(+)CD25(+) T cells may be a effective and safe tool for controlling allograft rejection and may help induce allograft tolerance. SN - 1879-1166 UR - https://www.unboundmedicine.com/medline/citation/22939904/In_vitro_expanded_CD4_+_CD25_high_Foxp3_+__regulatory_T_cells_controls_corneal_allograft_rejection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0198-8859(12)00540-X DB - PRIME DP - Unbound Medicine ER -