CD4(+)CD25(-)Nrp1(+) T cells synergize with rapamycin to prevent murine cardiac allorejection in immunocompetent recipients.

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-ß, 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.

[Comparison between Neuropilin-1(+)T cells and CD4(+)CD25(+) regulatory T cells].

AIM: To analyze the relationship between Nrp-1(neuropilin-1) positive T cells (Nrp-1(+)T cells) and CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+)Treg) and compare their immunoregulatory effects. METHODS: The expression of Nrp-1, CD4 and CD25 on the splenic T cells of BALB/c mice was detected by flow cytometry and Nrp-1(+)T cells and CD4(+)CD25(+)Treg were sorted. Then their effects of on NK cells killing B16-F10-luc-G5 melanoma cells were compared in vitro by bioluminescence imaging system. RESULTS: The expression of Nrp-1 on CD4(+)CD25(+)Treg was (27.28+/-1.17)%, which was significantly higher than that (1.63+/-0.08)% on CD4(+)CD25(-) T cells(P<0.01). Both Nrp-1(+)T cells and CD4(+)CD25(+)Treg inhibited the effect of killing NK cells on B16-F10-luc-G5 melanoma cells in vitro. At 6, 24, 48 and 72 h, the number of tumor cells in Nrp-1(+)T cell group was higher than that in CD4(+)CD25(+)Treg group(984+/-15 vs 931+/-4, 1015+/-14 vs 983+/-8, 1261+/-21 vs 1201+/-18 and 1323+/-38 vs 1256+/-18, respectively). There was significant statistical difference between the two groups at each time point (P<0.01). CONCLUSION: The proportion of CD4(+)CD25(+)Treg expressing Nrp-1 is high. Nrp-1(+)T cells show negtive immunoregulatory effect, which is more powerful than CD4(+)CD25(+)Treg. Nrp-1(+)T cells may be regarded as a new subgroup of Treg.