Diseases caused by reactions of T lymphocytes to in compatible structures of the major histocompatibility complex. I. Autoimmune hemolytic anemia

Abstract

Diseases caused by reactions of T lymphocytes to in com pat i ble structures of the major h istocom pa t i b i I i t y complex 1. Autoimmune hemolytic anemia"The capacities of various lymphoid cells from C57BL/10 donors t o induce antibodies against red blood cells (RBC) in (C57BL/10 x DBA/2)Fl recipients were compared: cortisone-resistant thymocytes were more potent inducers than spleen cells, and bone marrow cells were ineffective. This established a need for parental T lymphocytes in the induction of Coombs-positive hemolytic anemia by the graft-versus-host reaction (GVHR). Since some of the anti-RBC antibodies carried the Igc allotype specific for the F1 host, they were autoantibodies.When antibodies were eluted from the erythrocytes of F1 mice undergoing the GVHR (GVH F l mice) and subsequently tested against normal RBC in the indirect Coombs' test, the Igc allotype was demonstrable even on those antibodies found t o react with RBC of the donor strain (C57BL/10). In addition, reactions with normal intact RBC of other strains and species were noted. Anti-RBC antibodies belonged t o all Ig classes and subclasses that were tested (IgG1, k G z a , k G z b , IgA, and IgM).By means of histocompatibility typing it was shown that the overwhelming majority of lymphoid cells from GVH animals were host cells; most of these host cells were Thy-1.2-negative. In several GVH F1 mice Coombs-positive erythrocytes were demonstrated for periods of more than 5 months; Igc-positive anti-RBC antibodies were detected for periods up t o 3 months. When an additional injection of parental T cells was administered t o GVH F1 mice, which had become Coombs-negative in the course of the GVHR, new anti-RBC antibodies appeared. In contrast t o F 1 B cells, T cells of the F1 host were not needed for autoimmunization as shown by the induction of anti-RBC autoantibodies in F1 recipients that were depleted of autologous T cells prior t o the administration of parental T cells.When (C57BL/10 x DBA/2)Fl mice were back-crossed into strain C57BL/10 and the offsprings injected with C57BL/10 (H-2bb) lymphoid cells, most of the H-2 heterozygous (H-2bd) back-crosses developed Coombs'-positive hemolytic anemia, whereas none of the H-2 homozygous (H-2bb) ones did.The most likely explanation of these results is that anti-RBC autoantibodies were induced by a persistent reaction of parental T helper cells to incompatible H-2 structures on normally present autoreactive F l B cells. The hypothesis is proposed that reactions of T lymphocytes against virally or chemically altered structures of the major histocompatibility complex may lead t o autoimmunization also in nonchimeric individuals.

Capacity of genetically different T lymphocytes to induce lethal graft-versus-host disease correlates with their capacity to generate suppression but not with their capacity to generate anti-F1 killer cells. A non-H-2 locus determines the inability to induce lethal graft-versus-host disease.

“…Another possible outcome of the GVHR is a chronic GVHD which can lead to different conditions, such as lymphadenopathy (5,6), immune complex glomerulonephritis (6,7), and formation of multiple autoantibodies (8)(9)(10)(11). Previous analyses performed in nonirradiated Fa mice have shown that there are two minimal, essential requirements for the induction of the symptoms of chronic GVttD: immunocompetent T lymphocytes must be present in the donor cell inoculum and they must be able to react to incompatible H-2 structures of the recipient (5-7, 9, 11).…”

Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. I. Alloreactive suppressor cells rather than killer T cells appear to be the decisive effector cells in lethal graft-vs.-host disease.

“…Ig Allotype. Antisera specific for the Ig-I b allotype of B10 and the Ig-1 c allotype of DBA/2, respectively, were prepared as described (23). The anti-Ig-1 c serum was used at a constant dilution of 1 in 3 and the anti-Ig-1 h serum at a constant dilution of 1 in 9.…”

Rheumatoid arthritis--a virus disease?

“…These examples illustrate the general principle that a wide range of transient viral infections could initiate immune reactions that might interact with structural components of host cells such as histocompatibility antigens or viral proteins incorporated in cell membranes. Moreover, T lymphocyte reactions against histocompatibility antigens altered by virus infection could lead to true autoimmune reactions (Gleichmann and Gleichmann, 1976). Viral persistence in lymphoreticular cells (Fig.…”