Abstract
Rat skin grafted onto immunosuppressed mice is resistant to mouse anti-rat serum during the first 7-10 d after transplantation. It gradually acquires susceptibility, reaching a peak of sensitivity at 14-16 d after grafting. The grafts remain sensitive to antiserum, though at decreasing levels for an additional 3 wk, and grafts that persist beyond that time are resistant to antiserum for as long as they survive. In the study reported here, it is shown that the initial period of resistance to antiserum is due to factors acting locally within the graft and is entirely uninfluenced by the regimen of immunosuppression or the protective dressings that are used. After administration of antiserum, deposits of the injected immunoglobulin and of endogenous C3 are found on the luminal surfaces of graft vessels, although no significant tissue damage is observed. Rat skin that has become highly sensitive to antiserum 14-16 d after transplantation loses that sensitivity if it is regrafted to a new recipient, and then regains it 8-10 d later. Thus, the resistance of freshly grafted skin to antisera is associated with the process of healing into place, a conclusion that is supported by the observation that the intracutaneous administration of antisera to rats causes intense local inflammation and necrosis. The skin is therefore sensitive just before it is removed for grafting, but temporarily loses sensitivity thereafter. Resistance to antiserum during the first 3 or 4 d after transplantation is probably attributable to the fact that at that time grafts are vascularized poorly if at all. The state of resistance extends for several days after vascularization of the graft takes place and is then only gradually lost, a phenomenon that seems to be associated with the resistance of newly formed and regenerating blood vessels to vasoactive substances. This view is in accord with and, indeed, supports the idea that the induction of vascular injury is an essential step in antisera-mediated damage to tissue grafts.
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Selected References
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