Induction of dominant transplantation tolerance by an altered peptide ligand of the male antigen Dby
J. Clin. Invest. Tse-Ching Chen, et al. 113:1754 doi:10.1172/JCI20569 [
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Figure 5The 490R Ø H APL induces dominant transplantation tolerance in vivo. (
A) Long-term acceptance of syngeneic male skin grafts by female A1 ∞ RAG1–/– mice treated with five doses of 20 μg of 490R Ø H (
n = 16) (filled squares). All control mice receiving the cognate Dby peptide rejected their grafts with a mean survival time of 12 days (
n = 7) (filled inverted triangle), as did 10/14 mice treated with PBS alone (filled triangles). The results presented are pooled from three independent experiments. (
B) Mice rendered tolerant by administration of 490R Ø H (
n = 5) fail to reject existing and fresh skin grafts from male donors when infused with 107 T cells from naive A1 ∞ RAG1–/– mice (filled triangle). The same number of T cells administered to control RAG1–/– mice (
n = 5) rapidly mediated graft rejection (filled squares). (
C) Neutralization of IL-10 activity fails to abrogate tolerance induced by 490R Ø H. Mice tolerant of male skin grafts were treated with 1B1.2, specific for the IL-10R (
n = 10) (filled triangle) or an isotype-controlled mAb (
n = 10) (filled inverted triangle) before being infused with 5 ∞ 106 naive A1 ∞ RAG1–/– splenocytes and a fresh male skin graft. The same number of naive splenocytes induced rapid rejection of male skin grafts when infused into control RAG1–/– recipients (
n = 5) (filled squares).