title: CD4(+)CD25(-)Nrp1(+) T cells synergize with rapamycin to prevent murine cardiac allorejection in immunocompetent recipients.
abstract: Besides CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), other immunosuppressive T cells also participated in the regulation of immune tolerance. Reportedly, neuropilin-1 (Nrp1) might be one of the molecules by which regulatory cells exert their suppressive effects. Indeed, CD4(+)CD25(-)Nrp1(+) T cells exhibit potent suppressive function in autoimmune inflammatory responses. Here we investigated the specific role of CD4(+)CD25(-)Nrp1(+) T cells in the setting of the transplant immune response. Through MLR assays, we found that CD4(+)CD25(-)Nrp1(+) T cells suppressed the proliferation of naive CD4(+)CD25(-) T cells activated by allogeneic antigen-stimulation. Adoptive transfer of CD4(+)CD25(-)Nrp1(+) T cells synergized with rapamycin to induce long-term graft survival in fully MHC-mismatched murine heart transplantation, which was associated with decreased IFN-γ, IL-17 and increased IL-10, TGF-β, Foxp3 and Nrp1 expression in the grafts. Importantly, our data indicated that CD4(+)CD25(-)Nrp1(+) T cell transfer augments the accumulation of Tregs in the recipient, and creates conditions that favored induction of hyporesponsiveness of the T effector cells. In conclusion, this translational study indicates the possible therapeutic potential of CD4(+)CD25(-)Nrp1(+) T cells in preventing allorejection. CD4(+)Nrp1(+) T cells might therefore be used in bulk as a population of immunosuppressive cells with more beneficial properties concerning ex vivo isolation as compared to Foxp3(+) Tregs.
authors.affiliation: Organ Transplant Center, Organ Transplant Institution of PLA, The 309th Hospital of PLA, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.forename: Shanjuan
authors.initials: S
authors.lastname: Hong
authors.forename: Bingyi
authors.initials: B
authors.lastname: Shi
authors.forename: Jesper
authors.initials: J
authors.lastname: Kers
authors.forename: Zhouli
authors.initials: Z
authors.lastname: Li
authors.forename: Xiangke
authors.initials: X
authors.lastname: Pei
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D007121:Immunocompetence; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency*; D051379:Mice; D039942:Neuropilin-1 / Q000172:deficiency*; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D039942:Neuropilin-1; D020123:Sirolimus