Gyözö Petrányi

The genetic control of natural killer cell activity and its association with in vivo resistance against a moloney lymphoma isograft

Spleens of normal young mice of certain strains contain lymphocytes that can kill strain A-derived YAC-1 lymphoma cells in a51Cr release cytotoxic assay in vitro. We have previously classified mouse genotypes as high or low reactors, according to their responses in this test. In vivo resistance to small numbers of YAC ascites lymphoma cells is correlated with in vitro cytolytic activity. In vitro and in vivo tests were carried out on the same individual (A x C57BL)F1 x A backcross mice. Natural in vitro killer cell activity appeared to be under polygenic control, including a strong H-2-linked factor. No linkage was found with five different isozyme loci, with theIg-l locus or with C5 serum activity. Also in vivo resistance showed strong linkage with theH-2 complex. In (A x CBA)F1 x A backcross mice, a weak linkage was found with the coat color locusC. There was a correlation between in vitro killer activity and in vivo resistance in the same backcross mice. In vivo resistance was particularly strong in mice that combined theH-2b-linked resistance factor with a high cytolytic activity in vitro.

Genetic control of “natural” killer lymphocytes in the mouse

Spleens from normal young mice contain lymphocytes that can kill certain in vitro grown Moloney lymphoma lines in a51Cr-release cytotoxicity test. A lymphoid cell without detectable T- or B-cell markers was previously shown to be responsible. Killing activity shows a marked dependence on the genotype of the donor mouse. When tested against a YAC line of strain A origin maintained in vitro spleens of A, A.CA, and A.SW mice had low activity, whereas CBA, C3H, C57L, and C57Bl spleens were highly active. In semisyngeneic F1 crosses with strain A as one parent, reactivity resembled the opposite parental strain. Thus, (A×CBA)F1, (A×C3H)F1, (A×C57L)F1, and (A×C57Bl)F1 were reactive, whereas A×A.CA showed no significant activity. Analysis of the reactivity in (A×C57Bl)F1×A backcross mice suggests that multiple genes are involved. Preliminary linkage analysis suggests at least oneH-2 linked factor. Another gene appears to be linked to theB (black) locus.

Association between the lack ofHLA-DQw6 and the low incidence of multiple sclerosis in Hungarian Gypsies

In order to address the contradiction existing between high occurrence of HLA-DR2 and low incidence of MS in Gypsies, the distribution of the two subtypes of DQwl was determined in a Hungarian Gypsy population

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin.

Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy.

Mixed lymphocyte culture--evidence that pretransplant transfusion with platelets induces FcR and blocking antibody production similar to that induced by leukocyte transfusion.

Experimentation clinique: les transfusions de plaquettes purifiees peuvent induire un «facteur bloquant» efficace avant transplantation (renale)

Autoimmune-associated HLA-B8-DR3 haplotypes in Asian Indians are unique in C4 complement gene copy numbers and HSP-2 1267A/G

The classical AH8.1 (HLA-A1-B8-DR3-DQ2) is the most common Caucasian haplotype, associated with several autoimmune diseases, immunologic hyperreactivity and rapid progression to the acquired immunodeficiency syndrome. However, in Asian Indians, there are multiple unique B8-DR3 haplotypes that are associated with autoimmunity and differ significantly from the common Caucasian AH8.1. The Indian HLA-A1-B8-DR3 is therefore referred to as an AH8.1 variant. The aims of this study were to compare C4A and C4B copy numbers and to identify alleles in HSP70-2 and LTA in these haplotypes. The Indian B8-DR3 haplotypes differ from the Caucasian AH8.1 at C4A and HSP70-2 loci. The Indian B8-DR3 haplotypes have 1 copy each at C4A and C4B, while the Caucasian AH8.1 has 1 copy at C4B but no C4A gene. Moreover, the Indian and Caucasian B8-DR3 haplotypes had HSP70-2 1267 *A, and *G alleles, respectively. By contrast, the LTA 252 *G allele occurred both in the Indian and Caucasian haplotypes. The Indian haplotypes also contained Bf*F and TNF-308*G that were different from the Caucasian equivalents Bf*S and TNF-308*A. These differences and previous studies support the hypothesis that B8-DR3-DQ2 haplotypes in Asian Indian population might have originated independently of Caucasian AH8.1 selectively through recombination and mutations. Because autoimmune disease associations are shared among these otherwise diverse haplotypes, these data strongly suggest that some shared component(s) of all these associated haplotypes may be playing a key role in such associations.

Selective effect of noncytotoxic blocking alloantibodies produced after platelet transfusions on MLC, and mitogen and soluble antigen-induced responses of human lymphocytes

The transfusion of blood components (buffy coat and platelets) may induce characteristic alloimmune response or suppressive regulation that have, in certain cases, a beneficial effect on allograft survival. The blocking effect of the sera of donors immunized with platelets on mixed lymphocyte culture and on the response of lymphocytes to mitogen as well as soluble antigen (PPD, tetanus toxoid) stimulation was studied. Six sera from 7 volunteers displayed a strong and significant nonspecific MLC blocking effect that was detectable on the 10th day following the second platelet transfusion (PT). Incubation of isolated stimulator and effector cell population with this “blocking sera” showed that the latter are involved in the mediation of suppression in the MLC test. This inhibitory effect is associated with the serum IgG fraction lacking any correlation with either class I or class II specific cytotoxic antibodies. Selective blocking behavior was found on transformation activity induced by mitogens or soluble antigens. Thus, sera of platelet-transfused volunteers decreases the responsiveness of lymphocytes to phytohemagglutinin, while the response to concanavalin A, tetanus toxoid, and PPD was not suppressed. Separate treatment of T and B lymphocyte populations and monocytes with the blocking sera showed that only T and B lymphocytes are targets, and not the monocytes for the inhibition in the case of PHA-induced proliferation. Indirect evidence may support the notion that MLC-inhibiting and FcR-blocking antibodies may be analog products of a regulatory alloimmune response induced by leukocytes that are partially responsible for the beneficial transfusion effect in organ transplantation.

Detection of Activation Antigens on Chronic Lymphocytic Leukaemia Cells.

The peripheral blood mononuclear cells of patients with chronic lymphocytic leukaemia were characterized by the presence of a variety of cell surface differentiation antigens. The cells of 20 patients were found to be of B-cell phenotype when studied with antibodies directed against CD19, CD20, HLA-DR and sIg. Furthermore, a significant percentage of the cells gave a positive reaction with the monoclonal antibody to CD5. On the other hand, the CLL-cells did not express the CD21 antigen (C3d receptor, EBV receptor). We studied in parallel the presence of various activation antigens using 19 monoclonal antibodies grouped into 7 clusters (CD25, CD30, CD40, CD69, CD70, CD39, CD71). A significantly higher percentage of the CLL cells expressed activation antigens than lymphocytes from healthy controls. The percentage of CD3/HLA + DR + cells, compared to the healthy control lymphocytes was not increased in the CLL patients, and the activated cells in CLL were found to have characteristics of B-cells. Based on these results, we suggest that the CLL cells, like the cells in Hodgkins disease and T-cell lymphoma, are not resting, but activated B-cells or the neoplastic abberrants of activated cells.

The Results of 1009 Kidney Transplantations Performed in Hungary

Kidney transplantation is a widely used method throughout the world for the treatment of end-stage renal disease. Following the pioneering work of Szeged Medical University Hospital and Miskolc District General Hospital, the first successful kidney transplantation in Hungary was performed at the Department of Transplantation and Surgery at Semmelweis Medical University on November 16, 1973. This patient is still alive with a functioning kidney graft after 21 years. We report herein our review of the global results of Hungarian kidney transplantation. Hungary is a medium-developed country with a population of over 10 million where the gross national product is about 4000 U.S. dollars per person per year. In Hungary there are 49 dialysis centers, 4 immunological laboratories, and 4 transplantation centers.

P733 - Association between long term kidney Graft survival and the presence of pre transplant cytotoxic anti-HLA and/or non-MHC “Fe-GAMMA-RII blocking” (ANTI-TLX) alloantibody

One hundred kidney graft recipients were analysed retrospectively with regard to the presence of Fc gamma RII (EAI) blocking or cytotoxic HLA antibody induced by pretransplant transfusion. Previous studies suggested that transfusion induces the production of EAI blocking antibody which may have specificity to TLX/CD46/MCP alloantigens. A superior graft survival (65%/9 yr) was found in the presence of EAI alloantibody compared to graft survival in the absence of this antibody (40%/9 yr). Further analysis showed the following survival rates in relation to the combined appearance of HLA cytotoxic and EAI antibody (EAI positive, HLA negative 67%/9 yr; EAI positive, HLA positive 60%/9 yr; EAI negative, HLA positive 0%/9 yr; EAI negative, HLA negative 40%/9 yr). There was striking low graft failure in the first 6 months in patients with EAI antibody. Taking into consideration that the HLA B/DR mismatching grade in all various groups were the same and no considerable difference was found in association to graft survival, the presence or absence of alpha EAI (anti-TLX) antibody solely seems to have superior or additional effect on graft survival as compared to HLA matching.