ABSTRACT
In 1962 Silverman and Chin1 reported that some radiation chimeras they had constructed rejected skin grafts from the bone marrow cell (BMC) donor without losing BM chimerism. The model was a xenogeneic one, lethally irradiated C57BL mice restored with SpragueDawley rat BMC, and the authors were not the first to report that chimeras do not always accept donor strain skin grafts; in 1959 Billingham and Brent2 had reported that strain A mice given (C57BL x CBA)Fi hybrid spleen cells (SC) at birth became stable BM chimeras that accepted CBA but not C57BL skin grafts, a phenomenon they referred to as “split tolerance.” However Silverman and Chin were the first to propose an explanation for the effect based on skin-specific histocompatibility (H ) antigens. If the hematopoietic system of the BM chimera developed in the absence of donor skin, the chimeras should not be tolerant to donor skin-specific alloantigens; donor skin grafts therefore would be viewed as foreign and rejected. Based on “the long time required for completion of the rejection” (an average of 20-61 days in different experiments) Silverman and Chin likened the skin-specific reactions they observed to reactions against minor H antigens like H3 and HY. 1
In 1968 Boyse and Old3 also proposed an explanation for “the loss of skin allograft tolerance by chimeras” based on skin-specific “Sk” antigens; the term later was changed to “Skn” to avoid a nomenclature conflict with the scaly skin mouse mutation, Sk.4 Boyse et al5,6 found histogenetic substantiation for the Skn hypothesis: stable BM chimeras constructed by lethally irradiating C 57BL/6 (B6 ) mice and restoring them with (B 6 x A)Fi (B6 A) hybrid SC or BMC always accepted B6 skin grafts but consistently rejected both B6 A and A skin grafts in 2 -4 weeks. However, rejection was considerably delayed if the skin grafts were transplanted immediately after BM restoration rather than some weeks later, and rejection was prevented altogether if the hosts were given an injection of A strain epidermal cells (EC) at the time of BM restoration and 10 weeks later. The interpretation was that loss of self-tolerance to Skn antigens was averted if the hosts were provided with a constant source of donor strain skin cells.
