Bone marrow-derived cells are responsible for stimulating I region-incompatible skin graft rejection

By using bone marrow radiation chimeras as skin graft donors, we have evaluated the relative contribution of bone marrow-derived cells to allograft immunogenicity in both I region only and whole H-2-disparate strain combinations. When grafted on A.TH mice, skin from A.TH → A.TL bone marrow chimera donors showed markedly prolonged survival times compared with (1) normal A.TL skin, (2) A.TL → A.TL skin, or (3) skin from irradiated A.TL mice. A.TH → A.TL skin was accepted indefinitely on (A.TH × B10)F₁ mice whereas normal A.TL skin was promptly rejected. Thus, in the I region-only-disparate strain combinations, the bone marrow-derived cell in donor skin appears to be entirely responsible for skin graft immunogenicity. Furthermore, these data indicate a lack of epidermal specific histocompatiblity antigens mapping in the I region. In contrast, skin from A → (B6 × A)F₁ chimeras was rejected in the same time as normal (B6 → A)F₁ skin when grafted onto A mice. Immunoprecipitation and polyacrylamide gel electrophoresis of epidermal Ia confirmed that host Ia⁺ cells were absent in A → (B6 × A)F₁ skin. This demonstrates that allogeneic bone marrow-derived Ia⁺ cells are not required in donor skin for allograft immunogenicity across whole H-2 differences. We were unable to induce graft rejection of chimeric skin by creating chimeras whose skin was compatible but bone marrow incompatible (either whole H-2 or I region only) with the skin graft recipient. We interpret these results to indicate that bone marrow-derived Ia⁺ cells in donor skin are sufficient by themselves but not necessarily required for allograft immunogenicity if appropriate antigenic differences are expressed on the remainder of the epidermal cells. These results are consistent with current evidence implicating the Langerhans cell as the relevant bone marrow-derived cell responsible for skin graft immunogenicity.