Acute Destruction by Humoral Antibody of Rat Skin Grafted to Mice

Abstract

We have described briefly the acute destruction of rat skin xenografts after injections of their hosts with antisera specifically reactive with graft antigens (1). The rat skin had been grafted to mice whose immune responses were suppressed by removal of the thymus and treatment with rabbit antimouse lymphocyte serum. When these xenografts had healed completely into their beds and could be fully expected to survive for one or more additional weeks, the mice were injected with antirat serum that had been prepared in mice or in rabbits. Signs of graft damage were evident as early as 10 rain after the injection of serum, and in most animals so injected the grafts were completely destroyed within 24-48 h. Studies in which fixed sections of grafts were examined microscopically revealed the early occurrence of edema and infiltration of the grafts with polymorphonuclear leukocytes followed by extreme dilatation and congestion of small vessels, hemorrhage, and necrosis (2). Both gross and microscopic aspects of these reactions were similar to those described for Arthus reactions and other forms of immune vasculitis in rabbits and guinea pigs (3, 4). Reactions of the latter types have been the subject of intensive investigation in recent years, and a good deal has been learned of the pathways leading to tissue damage in these reactions (5). We have looked, therefore, for similar mechanisms in the destruction of skin grafts that is mediated by humoral antibodies, and the experiments to be described here were designed primarily to evaluate the roles of granulocytes and the plasma complement system, agents which are known to be involved in a variety of lesions that are initiated through immunological reactions. Materials and MethodsExperimental System.--The basic test system has been described in detail (2). Adult mice were thymectomized 1-2 wk before receiving grafts of rat ear skin. Rabbit antimouse lympho-

B Lymphocytes Differentially Influence Acute and Chronic Allograft Rejection in Mice

“…Xenotransplants are also rejected normally in Xid mice (51), and BALB/C skin is rejected normally in agammaglobulinemic B10.BR mice treated chronically with anti-IgM serum to deplete B cells (52). Reduced allograft-specific Ab quantities following B cell depletion did not appear to affect skin graft (Figure 5A–B) or cardiac allograft (Figure 4) rejection, even though the addition of exogenous allograft-specific Ab is capable of inducing skin graft destruction (53, 54). Further, allograft-specific Abs can cause pathological lesions in mouse cardiac allografts (55) and allograft rejection in immunosuppressed mice (11, 15, 16).…”

Role of complement and NK cells in antibody mediated rejection

“…As mentioned in the previous section, Winn and co-workers conducted a series of experiments with mice receiving rat skin grafts [4]. Rejection was shown to be dependent on complement, as judged by the inability of non-complement fixing antibodies or F(ab′) 2 fragments to mediate rejection, prevention by depletion of complement by cobra venom factor and resistance to rejection in C5 deficient recipients.…”

“…Therefore, antibody was not thought to mediate rejection. In contrast, Winn and co-workers showed that if rat skin grafts were allowed to heal in over 2 weeks in immunosuppressed mice, grafts became highly susceptible to acute rejection by adoptive transfer of mouse anti-rat serum with immediate effects evident 10 min after serum administration and total graft loss in 1–2 days [4]. Gerlag and co-workers confirmed the sensitivity of healed in skin grafts to donor specific antiserum in analogous studies in mouse skin allografts [5].…”

Glomerular Protein Filtration in Normal and Nephritic Rats1,2

“…2). The reason most likely is a great individual variability in mobilising the different mediator systems which are triggered by the antigen antibody reaction at the glomerular basement membrane (25)(26)(27).…”