Lysis of antibody-coated cells by platelets.

Antibody-coated erythrocytes are lysed by murine C5- whole blood but not by plasma separated from such blood. The lytic activity has been shown to derive from platelets that attach to sensitized cells probably through membrane receptors for C3b. Whole blood or platelet-rich plasma (prp) obtained from mice that have been treated with purified cobra venom factor has little or no activity unless it is fortified with fresh C5- plasma. Lysis is observed only if the reactants are incubated at 37 degrees C and mechanical shaking is practiced, at least intermittently, throughout the period of incubation. Adherence of platelets and subsequent lysis are mediated by antibodies of a variety of immunoglobulin classes, including those that fail to mediate complement-dependent lysis. Platelet-mediated lysis is limited to cells to which the platelets adhere; 51Cr labeled, unsensitized cells that are mixed with prp and sensitized, unlabeled cells do not release 51Cr. Normal murine lymphoid cells and ascites tumor cells of mice, rats, and guinea pigs were apparently unaffected by sensitization and incubation with prp. However, because adherence of platelets to these sensitized cells was not observed, it is not clear whether the cells are resistant to the lytic action of platelets or whether the conditions of incubation were unfavorable for the attachment of platelets to the surfaces of nucleated cells. The significance of the lytic reaction described here is not known but may lie in antibody mediated release of microbicidal substances from platelets.

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.

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.

Positive autologous crossmatches and a successful transplant with an HLA-identical, but not with an HLA-nonidentical, kidney.

A kidney graft from an HLA-nonidentical donor following a positive crossmatch in the presence of autoantibodies was rejected, but a subsequent graft from an HLA-A, B, C, DR-identical donor, also following a positive crossmatch, survives. Cytotoxic reactivity was present at 4 C and 37 C, and required complement. Sucrose gradient fractionation showed that most of the reactivity resided in the IgM fraction of the serum. Reactivity with donor T and B lymphocytes was not removed by absorption with platelets. Absorption with autologous lymphocytes failed to remove reactivity to lymphocytes of the first (non-HLA-identical) donor and T and B cells of another individual with the same HLA type as the first donor, although removing reactivity to T, but not to B cells of the second (HLA-identical) donor. This case demonstrates that the presence of a multitude of cold-reactive and warm-reactive T and B cell autoantibodies and non-HLA alloantibodies creates an immunological environment in which only the optimally matched graft will survive.

Total parathyroidectomy and autotransplantation in secondary hyperparathyroidism.

Sixteen patients with chronic renal failure and symptomatic secondary hyperparathyroidism underwent total parathyroidectomy. Sixteen to 25 fragments of parathyroid tissue measuring 1 cu mm were autotransplanted into the brachioradial muscle. Evidence of "take" of the autotransplant was present in all patients, although four patients still have hypocalcemia and require calcium and vitamin D supplementation. Three patients have experienced late diminution of autotransplant function. Symptomatic improvement occurred promptly in 15 of the 16 patients. Two patients with persistently elevated parathormone levels were treated by partial excision of the implant, and one patient whose autograft functioned inadequately was successfully treated by implantation of cryopreserved autologous parathyroid tissue. Total parathyroidectomy with autotransplantation of parathyroid fragments to the forearm is the preferred surgical procedure for secondary hyperparathyroidism.