Figure 1.
Induction of transplantation tolerance to syngeneic male skin grafts by HY peptides. (A) Intranasal administration of HYAbDby alone or with HYDbUty peptide induces indefinite survival of syngeneic male skin grafts. Survival of syngeneic male skin grafts placed 10 days after intranasal pretreatment of B6 females with 3 × 100 μg HY peptide: HYAbDby (n = 25; ○), HYDbUty (n = 38; ▵), both peptides (n = 7; ⋄), PBS control (n = 10; □). Significant differences from PBS control: P < .0001 for the HYAbDby and HYAbDby plus HYDbUty groups, P = .0059 for the HYDbUty group. Data pooled from 3 experiments. (B) Tolerance induced by intranasal peptide treatment is transplantation antigen specific. Survival times of each of 2 secondary skin grafts placed on HYAbDby peptide–pretreated B6 mice retaining primary syngeneic male skin grafts more than 270 days (n = 14): syngeneic male graft (○), (B6/EiJ×C3H.SW)F1 graft (•; P > .0001). Data pooled from 2 experiments. (C) Administration of 3 μg HYAbDby peptide can tolerize, whereas HEL peptide has no effect and LPS abrogates tolerance. Survival times of syngeneic male skin grafts on B6 females given intranasally 3 × 3 μgHYAbDby (n = 21; ○), 3 × 100 μg HEL peptide (n = 16; □) or 3 × 100 μg HYAbDby peptide plus 3 μg LPS (n = 7; ▪). Significant difference of HEL peptide from HYAbDby control is P > .001. (D) Induction of tolerance in (B6×CBA)1 females. Survival times of syngeneic male skin grafts on (B6×CBA)F1 females following pretreatment with PBS (n = 7; ○), HYEkDby (n = 7; ⋄) or HYAbDby (n = 7; •) peptides (3 × 100 μg). (E) Role of IL-10. Survival times of syngeneic male skin grafts on B6.IL10–/– mice given intranasally 3 × 100 μg HYAbDby peptide (n = 6; ○) or PBS (n = 3; □). P = .0018. (F) Effect of male hematopoietic cell grafting on subsequent male skin grafts. Survival times of syngeneic male skin grafts on B6 mice pretreated intranasally with 3 × 100 μgHYAbDby peptide (n = 8; ○) or PBS (n = 8; □) followed by challenge at day 10 with male spleen cells, and grafting with male skin 60 days later; P = .0001.