A new retroviral AIDS-like disease and/or acute leukemia induced in mice by alloimmune stimuli.

We have shown a new phenomenon demonstrating that BALB/c female mice mated to C57BL/6 males during a year (7-10 pregnancies) develop AIDS-like disease or acute leukemia after an additional immunization with fixed ConA activated paternal (C57BL/6) lymphocytes. The AIDS-like disease is sexually and vertically transmissible and easily transferable to intact BALB/c and C57BL/6 mice by filtered plasma of affected animals.

A new transmissible AIDS-like disease in mice induced by alloimmune stimuli.

The search for a suitable and reliable animal model for human AIDS that is easy to use on a large scale continues. Here we describe a new condition in mice that closely resembles human AIDS, namely, chronic lymphoproliferation with dramatic depletion of CD4-positive cells, progressive impairment of the immune responses, and Kaposi's sarcoma-like tumors or terminal B-lymphomas. The AIDS-like disease was primarily induced by mating BALB/c female mice to C57BL/6 males during a 1-year period (7-10 allogeneic pregnancies) followed by immunization with paternal lymphocytes. The disease is sexually and vertically transmissible, transferrable by cell-free plasma and is associated with autoimmune reactions to major histocompatibility complex antigens and CD4 cells. We hope that this becomes a model for studying the mechanisms of AIDS immunopathogenesis and immune-based treatment approaches.

Autoimmunity and counter-autoimmunity in the mechanisms of retrovirus-induced leukemogenesis.

The role of autoimmune mechanisms in the pathogenesis of retrovirus-induced leukemia was studied using as models different forms of Rauscher leukemia virus (RV) infection in mice of different strains. It was found that mice undergoing progressive course of leukemia ("progressors") produce (a) autoantibodies to a series of antigens intimately involved on immune response regulation (class II MHC antigens, cell surface markers of helper and suppressor T-lymphocytes and erythrocaryocytes, receptors for IL-2, etc.); (b) antiidiotypic antibodies which suppress both antiviral responses and autoimmune reactions against class I MHC antigens. Passive transfer of these antibodies into genetically resistant mice prior to RV inoculation breaks their resistance. Completely resistant C57BL/6 mice and mice undergoing "spontaneous" regression of leukemia ("regressors") were found to be genetically capable of (a) suppressing autoimmune reactions of "progressors" type by active synthesis of antiidiotypic antibodies; (b) producing autoantibodies to MHC class I antigens. Immunization with monoclonals to H-2Db as well as with "anti-autoimmune" antiidiotypes prior to RV infection leads to abrogation of appropriate immune reactions and development of leukemia in C57BL/6 mice.

[Autoimmune reactions against interleukin-2 receptors in patients with blood system diseases and in experimental Rauscher retrovirus leukemia]. / Autoimmunnye reaktsii protiv retseptorov dlia interleikina-2 u bol'nykh s nekotorymi zabolevaniiami sistemy krovi i pri éksperimental'nom retrovirusnom leikoze Raushera.

Apart from autoimmune reactions, antibodies to IL-2 receptors were identified in blood sera of linear mice during leukemogenesis. It is indicated that in the course of leukemia establishment, there can be demonstrated antibodies capable of blocking IL-2 receptors on the membrane of activated T lymphocytes and inhibiting IL-2-dependent proliferation of T cells. The blood sera of patients suffering from chronic lymphoid leukemia, acute lymphoblastic leukemia, lymphocytomas, pure red-cell aplasia, and aplastic anemia showed antibodies against IL-2 receptors. Out of the total number of 52 patients, 23 demonstrated those antibodies. The data obtained should be taken into account in the patients' management using IL-2.

[Antilymphocytic humoral autoimmune response of mice with developing Rauscher leukemia directed against group-specific retrovirus antigens]. / Antilimfotsitarnye gumoral'nye autoimmunnye reaktsii myshei s razvivaiushchimsia leikozom Raushera, napravlennye protiv gruppospetsificheskikh antigenov retrovirusov.

The methods of indirect membrane immunofluorescence, immunoenzyme analysis, complement-dependent cytotoxicity and sorption tests were used to demonstrate two types of humoral antilymphocytic autoimmune reactions at the early stage of the Rauscher leukemia in mice of BALB/c, BDF1 and C57B1/6 strains. The first one is directed against group-specific oncoviral antigens (p30, p15) expressed on the lymphocyte membrane of both intact mice and of those with leukemia, the second one is virus-independent and possesses strain specificity.

[Neoplastic form of chronic erythromyelosis (erythrosarcoma) with eosinophilia and cardiac lesions]. / Opukholevaia forma khronicheskogo éritromieloza (éritrosarkoma), protekaiushchego s eozinofiliei i porazheniem serdtsa.

The paper is concerned with a case history of a 24-year old man suffering from chronic erythromyelosis with erythrokaryocytic metaplasia of the peripheral lymph nodes, bone marrow, spleen, liver, heart and lungs. The hypereosinophilic syndrome and endocardial fibrosis caused diagnostic difficulties. A short-term effect after injection of the plasma from a patient with erythrocytic aplasia containing antierythroblastic antibodies was obtained, tumor tissue mass reduced. Later on courses of CAMP-therapy were initiated. The progression of disease resulted in the patient's death in 2 years.

[Autogenic anti-idiotypic suppression of autoimmune reactions--a new approach to immunotherapy of experimental leukemia]. / Autogennoe antiidiotipicheskoe podavlenie autoimmunnykh reaktsii--novyi podkhod k immunoterapii eksperimental'nykh leikozov.

Experimental Rauscher's virus erythroleukemia (RVE) was employed to study the immunologic mechanisms by which leukemia develops. Experiments were performed on inbred mice, genetically opposite to the disease induction, namely on highly sensitive BALB/c, resistant C57BL/6 and moderately sensitive BDFI animals. It is shown that RVE resistance is an immunologic phenomenon that results from the functioning of the antileukemic immune defence (ALID) aimed against the tumor-specific antigenic complex. Suppression of the ALID stems from autosuppression of the H-2 complex of the histocompatibility antigen system of T suppressors, which leads to the development of the onco-specific complex of autoimmune responses (OSCAR) and to the obligate development of RVE. The recovery of the ALID with OSCAR suppression and RVE regression is a consequence of the development of strictly specific antiidiotypic immune responses (antibodies AIT-anti-OSCAR). It is demonstrated that both passive administration of AIT-anti-OSCAR and induction of their active synthesis brings about a remission of RVE.

[Antibodies against interspecies erythrokaryocyte antigen in patients with partial red cell aplasia of the bone marrow]. / Antitela protiv mezhvidovogo antigena éritrokariotsitov u bol'nykh partsial'noi krasnokletochnoi aplaziei kostnogo mozga.

Immunofluorescense and cytotoxicity test in vitro were used to demonstrate specific antibodies in sera of 11 out of 19 patients with partial red cell aplasia (PRCA). The antibodies reacted with erythroblast cells from embryos and adult men, with bone marrow cells from a female patient suffering from acute erythroleukemia, with erythrokaryocytes of mouse embryos and cells of Rauscher's viral erythroleukemia. The results of cross adsorption and blockade of the immunofluorescent reaction of the sera of PRCA patients with antibodies against mouse erythroblast antigen bearing an interspecies determinant suggest that in the pathogenesis of PRCA there takes part an autoimmune reaction against specific interspecies antigen to erythrokaryocytes. This antigen is apparently similar to antigen against mouse erythroblast cells.

[Antigenic marker of human erythrokaryocytes similar to mouse erythroblastosis antigen]. / Antigennyi marker eritrokariotsitov cheloveka, skhodnyi s antigenom éritroblastov myshei.

Identical antigenic determinants are discovered on the surface of human erythrokaryocytes with antibodies against specific antigen of murine erythroblasts (Ag-Ed), previously revealed in study of Rauscher leukemia, in the immunofluorescent and cytotoxic tests. The antigen is present on the membranes of the majority of human embryonic liver and adult bone marrow nuclear erythroid cells, but is not found in fetal thymocytes, newborn kidney cells, adult human hepatic cells and in peripheral blood erythrocytes. Ag-Eb appears to possess an inter-species determinant, shared by mammalian nuclear erythroid cells, and may be used as their specific marker.