The vascular bed as the primary target in the destruction of skin grafts by antiserum. I. Resistance of freshly placed xenografts of skin to antiserum

Abstract

We have shown that both xenografts and allografts of rat skin can be acutely and severely damaged by antisera specifically reactive with graft antigens, and that in appropriate circumstances the phenomenon can be elicited routinely (1, 2). A matter of paramount importance among the variables that influence the occurrence of this form of immunologically mediated tissue damage is the interval of time between the placement of the grafts and the administration of antiserum (3). Contrary to widely held views on the special vulnerability of grafts that are healing into place, it has been found that antiserum injected at the time of grafting or within 5-6 d thereafter has little detectable influence on the course or time of survival of the transplanted skin. This period of insusceptibility is rapidly succeeded by a state of sensitivity to humoral antibody that, in immunosuppressed hosts, reaches a peak of intensity at about 14-16 d after grafting and persists at decreasing levels for an additional 3 wk. Grafts that survive beyond that period of time regain their resistance to antiserum, and this state is maintained for the duration of survival of the grafts.We have analyzed these changes in the responses of xenografts of skin to antisera, and we have found that the initial state of insensitivity differs substantively from that observed in long-standing grafts. We describe here the results of our studies on freshly placed grafts, and in a succeeding paper (4) we report on the mechanisms involved in the acquired resistance of grafts that have survived for relatively long periods of time. Materials and MethodsAnimals. B6AF1 and CAFa mice were purchased from The Jackson Laboratory, Bar Harbor, Maine. Lewis (LE) and (Le × BN)F1 hybrid rats (LBN) were obtained from Microbiological Associates, Walkersville, Md. CD rats were purchased from the Charles River Breeding Laboratories, Wilmington, Mass.Antisera. Rabbit anti-mouse thymocyte serum (RAMTS) 1 was prepared as described (5) or was obtained from Microbiological Associates. 13 pools of antisera were used, the least potent of which extended the mean survival time of rat skin grafts to 32.5 :t: ! 1 d. Rabbit anti-rat *

Monokine Induced by Interferon-γ (MIG/CXCL9) Is Derived from Both Donor and Recipient Sources during Rejection of Class II Major Histocompatibility Complex Disparate Skin Allografts

“…During rejection of Mig-deficient skin allografts, the chemokine protein was clearly present in the vascular endothelium of the lower dermis and was associated with cells around the vessels. These results are consistent with the neovascularization of the skin allograft by recipient endothelium [23][24][25] and the importance of this source of Mig in directing T-cell infiltration into the allograft. In contrast, Mig protein was not detected in vascular structures in the upper dermal vascular plexus of Mig Ϫ/Ϫ allografts and there was little to no detectable T-cell infiltration into this area of the allograft until late in the delayed rejection of the grafts.…”

Fetal porcine thymus engraftment, survival and CD4 reconstitution in αGal‐KO mice is impaired in the presence of high levels of antibodies against αGal

“…Neovascularized porcine neural tissue survives longer in immunoglobulin‐deficient mice than WT mice [46], supporting a role for antibodies in rejection. A role for xenoantibodies in rat skin xenograft rejection has also been demonstrated [47,48].…”

Role of complement and NK cells in antibody mediated rejection

“…They found a notable time dependence of susceptibility to antibody mediated rejection. Grafts were resistant to mouse anti-rat serum during the first 7–10 days after transplantation, but gradually became susceptible to immune serum and reached a peak of sensitivity at 14–16 days after grafting [21,22]. If the graft survived beyond that time, the graft once again became resistant to antiserum for as long as they survived [21].…”