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Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells.
Int Immunol. 2004 Aug; 16(8):1189-201.II

Abstract

Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to establish immunologic tolerance to non-self antigens. In vivo exposure of CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+) T(R) cells, which suppressed allograft rejection mediated by subsequently transferred naive T cells, leading to long-term graft tolerance. The expanded T(R) cells, which became CD25(low) in the absence of other T cells, stably sustained suppressive activity, maintained expression levels of other T(R) cell-associated molecules, including Foxp3, CTLA-4 and GITR, and could adoptively transfer tolerance to normal mice. Furthermore, specific removal of the T(R) cells derived from originally transferred CD25(+)CD4(+) T(R) cells evoked graft rejection in the long-term tolerant mice, indicating that any T(R) cells deriving from CD25(-)CD4(+) naive T cells minimally contribute to graft tolerance and that natural T(R) cells are unable to infectiously confer significant suppressive activity to other T cells. Similar antigen-specific expansion of T(R) cells can also be achieved in vitro by stimulating naturally present CD25(+)CD4(+) T cells with alloantigen in the presence of IL-2. The expanded CD25(+)CD4(+) T cells potently suppressed even secondary MLR in vitro and, by in vivo transfer, established antigen-specific long-term graft tolerance. Thus, in vivo or in vitro, direct or indirect ways of antigen-specific expansion of naturally arising Foxp3(+)CD25(+)CD4(+) T(R) cells can establish antigen-specific dominant tolerance to non-self antigens, and would also be instrumental in re-establishing self-tolerance in autoimmune disease and antigen-specific negative control of pathological immune responses.

Authors+Show Affiliations

Department of Experimental Pathology, Institute for Frontier Medical Sciences, Faculty of Medicine, Kyoto University, Japan.No 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

15237110

Citation

Nishimura, Eiji, et al. "Induction of Antigen-specific Immunologic Tolerance By in Vivo and in Vitro Antigen-specific Expansion of Naturally Arising Foxp3+CD25+CD4+ Regulatory T Cells." International Immunology, vol. 16, no. 8, 2004, pp. 1189-201.
Nishimura E, Sakihama T, Setoguchi R, et al. Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. Int Immunol. 2004;16(8):1189-201.
Nishimura, E., Sakihama, T., Setoguchi, R., Tanaka, K., & Sakaguchi, S. (2004). Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. International Immunology, 16(8), 1189-201.
Nishimura E, et al. Induction of Antigen-specific Immunologic Tolerance By in Vivo and in Vitro Antigen-specific Expansion of Naturally Arising Foxp3+CD25+CD4+ Regulatory T Cells. Int Immunol. 2004;16(8):1189-201. PubMed PMID: 15237110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. AU - Nishimura,Eiji, AU - Sakihama,Toshiko, AU - Setoguchi,Ruka, AU - Tanaka,Koichi, AU - Sakaguchi,Shimon, Y1 - 2004/07/05/ PY - 2004/7/9/pubmed PY - 2005/2/24/medline PY - 2004/7/9/entrez SP - 1189 EP - 201 JF - International immunology JO - Int Immunol VL - 16 IS - 8 N2 - Naturally arising CD25(+)CD4(+) regulatory T (T(R)) cells can be exploited to establish immunologic tolerance to non-self antigens. In vivo exposure of CD25(+)CD4(+) T cells from normal naive mice to alloantigen in a T cell-deficient environment elicited spontaneous expansion of alloantigen-specific CD25(+)CD4(+) T(R) cells, which suppressed allograft rejection mediated by subsequently transferred naive T cells, leading to long-term graft tolerance. The expanded T(R) cells, which became CD25(low) in the absence of other T cells, stably sustained suppressive activity, maintained expression levels of other T(R) cell-associated molecules, including Foxp3, CTLA-4 and GITR, and could adoptively transfer tolerance to normal mice. Furthermore, specific removal of the T(R) cells derived from originally transferred CD25(+)CD4(+) T(R) cells evoked graft rejection in the long-term tolerant mice, indicating that any T(R) cells deriving from CD25(-)CD4(+) naive T cells minimally contribute to graft tolerance and that natural T(R) cells are unable to infectiously confer significant suppressive activity to other T cells. Similar antigen-specific expansion of T(R) cells can also be achieved in vitro by stimulating naturally present CD25(+)CD4(+) T cells with alloantigen in the presence of IL-2. The expanded CD25(+)CD4(+) T cells potently suppressed even secondary MLR in vitro and, by in vivo transfer, established antigen-specific long-term graft tolerance. Thus, in vivo or in vitro, direct or indirect ways of antigen-specific expansion of naturally arising Foxp3(+)CD25(+)CD4(+) T(R) cells can establish antigen-specific dominant tolerance to non-self antigens, and would also be instrumental in re-establishing self-tolerance in autoimmune disease and antigen-specific negative control of pathological immune responses. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/15237110/Induction_of_antigen_specific_immunologic_tolerance_by_in_vivo_and_in_vitro_antigen_specific_expansion_of_naturally_arising_Foxp3+CD25+CD4+_regulatory_T_cells_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxh122 DB - PRIME DP - Unbound Medicine ER -