ALLOGENEIC RED BLOOD CELLS FAIL TO INDUCE HAEMAGGLUTINATING ANTIBODIES OR CELLULAR ALLOIMMUNITY IN RATS AND ARE IMMUNOSUPPRESSIVE

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Abstract

Summary

Purified rat red blood cells, which express the A region antigens of the major histocompatibility complex (MHC) with which anti-RT-1 (H-l; Ag-B) haemagglutinins combine, fail to stimulate the production of either haemagglutinating antibodies or cellular immunity in allogeneic hosts. Allogeneic red blood cells may in appropriate circumstances be mildly immunosuppressive. Intraperitoneally injected allogeneic red blood cells persist in the host circulation for several weeks. The immune response to skin allografts does not accelerate the destruction of circulating donor strain red blood cells, although the administration of alloantiserum with a high haemagglutinin titre can do so. The manner in which allogeneic red blood cells effect immunosuppression is unknown. Approximately 75% of the red blood cells administered i.v. to nonimmune allogeneic hosts are destroyed, by mechanisms unknown, during the first 6 days after injection. By contrast, about one-half of this number of red blood cells are destroyed by syngeneic hosts during the same period.

Red blood cells and platelets in rodents are probably similar in expressing A region (rats) or K-D region (mice) antigens of the MHC, in being nonimmunogenic by themselves and in their capacity for effecting limited immunosuppression. If human platelets have similar attributes, the administration of platelets bearing the appropriate HLA-A, B, and C antigens might be a useful adjunct to conventional immunosuppression in the management of allografts in man. Likewise, the platelet component of blood transfusions might account for their beneficial effect in some renal allograft recipients.

Allografts that are incompatible with their hosts in respect to MHC antigens usually stimulate the production of haemagglutinating antibody in rats (1, 2). On the basis of two recombinants (3, 4) the rat MHC has tentatively been divided into two regions, A and B (5). The A region determines erythrocyte and lymphocyte alloantigens and is only weakly stimulatory in the mixed lymphocyte reaction. It appears to be the homologue of the K and D regions of the mouse H-2 complex. The B region contains at least two Ir genes and also determines lymphocyte alloantigens that are possibly confined to B lymphocytes. There is no evidence that the B region determines red blood cell antigens. This communication records that A region antigens on red blood cells, although targets for haemagglutinating antibodies, fail to stimulate haemagglutinin production. Additionally, in appropriate circumstances allogeneic red blood cells may be immunosuppressive.

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