DC_VIPs impair allogeneic antigen-specific responses of donor CD4⁺ T cells in transplanted mice by inducing the generation of Tr cells in the graft. GVHD was induced in recipient Balb/c (H-2^d) mice by allogeneic transplantation of BMS from B6 (H-2^b) mice. Two days after transplantation, recipients were given injections of medium (none) or BM-DCs from Balb/c (H-2^d) generated in the absence (DC_controls) or presence (DC_VIPs) of VIP. (A) Donor I-K^b cells isolated from recipient spleens 5 days after transplantation were assayed for phenotype and cytokine profile by flow cytometry. Data are expressed as percentage positive cells (n = 8). P < .01 untreated and DC_controls recipients versus DC_VIPs group for any T-cell population. (B) Donor I-K^bCD4⁺ cells isolated from recipient spleens were cultured with medium alone (none) or with mature DC (H-2^d) in the presence or absence of IL-2 at a T-cell/DC ratio of 10:1, and the proliferative response was determined (n = 8). ^*P < .01 versus untreated recipients. (C) Cytokine concentrations in sera obtained 5 days after transplantation were assayed by ELISA (n = 8). ^*P < .01 versus untreated recipients. (D) Untreated recipients (•) or recipients that were given injections of DC_VIPs and treated with control immunoglobulin (○), anti-IL-10 (▾), anti-TGF-β (▿), or anti-CD25 mAbs (▪), or a combination of all 3 mAbs (□; 12 mice/group). P < .01, control immunoglobulin-treated DC_VIPs recipients versus any other group.