ABSTRACT
In this study, we have demonstrated the occurrence of IgG class noncytotoxic, lymphocyte Fc gamma-receptor-blocking antibodies in a proportion of sera obtained from transfused uremic patients. The presence of these antibodies was not found to correlate with subsequent renal allograft survival. Serum fractionation studies did however reveal a striking correlation between graft survival and Fc gamma-receptor blocking mediated by a serum factor(s) with a sedimentation coefficient of greater than 19S. The precise nature of this factor remains to be clarified.
Subject(s)
Blood Proteins/physiology , Graft Survival , Isoantibodies/immunology , Kidney Transplantation , Receptors, Fc/immunology , Blood Transfusion , Dinitrochlorobenzene/immunology , Humans , Immune Tolerance , Immunity, Cellular , Molecular Weight , Receptors, IgG , Rosette FormationABSTRACT
Various batches of intravenous gammaglobulin (IV-IgG) were found to contain antibodies with the capacity to block human peripheral blood lymphocyte receptors for the Fc region of IgG i.e., Fc gamma-receptors (Fc gamma Rs). The level of Fc gamma R-blocking produced was found to vary considerably from batch to batch and from lymphocyte donor to donor. IgG purified from normal human serum pooled from only 20 donors was also found to produce significant Fc gamma R-blockade. Analysis of the individual contributors to this normal IgG pool indicated that Fc gamma R-blocking antibodies may in fact be auto-antibodies.
Subject(s)
Immunoglobulin G/immunology , Lymphocytes/immunology , Receptors, Fc/immunology , Adult , Alkylation , Antibody-Dependent Cell Cytotoxicity , Female , Humans , In Vitro Techniques , Male , Oxidation-Reduction , Receptors, IgG , Rosette Formation , Sex Characteristics , UltracentrifugationABSTRACT
In this study we have shown that transfusion-induced Fc gamma R-blocking antibodies have the capacity to react with various cell types which are known to possess this receptor i.e., lymphocytes (T and B cells), polymorphs and platelets. In contrast we were unable to demonstrate any reactivity with K (or NK) lymphocytes or with monocytes. The spectrum of cellular reactivity exhibited by these antibodies suggests that their effect on the immune system may be complex.
Subject(s)
Antibodies/immunology , Blood Transfusion , Receptors, Fc/immunology , Adolescent , Adult , Aged , Antibody-Dependent Cell Cytotoxicity , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Binding, Competitive , Blood Platelets/drug effects , Female , Humans , Immunoglobulin G/pharmacology , Male , Middle Aged , Neutrophils/cytology , Neutrophils/immunology , Phagocytosis/drug effects , Platelet Aggregation/drug effects , Receptors, IgG , Rosette Formation , T-Lymphocytes/cytology , T-Lymphocytes/immunologyABSTRACT
In this study we have shown that IgG class, noncytotoxic, Fc gamma-receptor blocking antilymphocyte antibodies can de detected in a high proportion of patients who have previously been exposed to alloantigens, i.e. multiple transfused uraemic patients, haemophiliacs and male homosexuals. These antilymphocyte antibodies appear to cross-react with human spermatozoa. Monomeric IgG preparations from these patients were also found to significantly impair T-cell responsiveness in vitro. Depression of cell mediated immunity by these antibodies may contribute to prolonged graft survival in uraemic patients but may also predispose to infection.
Subject(s)
Antibodies/analysis , Immune Tolerance , Isoantigens/immunology , Lymphocytes/immunology , Receptors, Fc/immunology , Acquired Immunodeficiency Syndrome/immunology , Adolescent , Adult , Aged , Agglutination Tests , Antilymphocyte Serum/analysis , Blood Transfusion , Cross Reactions , Female , Hemophilia A/immunology , Homosexuality , Humans , Immunity, Cellular/drug effects , Immunoglobulin G/analysis , Isoantigens/administration & dosage , Lymphocyte Activation , Male , Middle Aged , Receptors, IgG , Rosette Formation , Spermatozoa/immunology , T-Lymphocytes, Regulatory/immunology , Uremia/immunologyABSTRACT
In this study, we have isolated membranelabile Fcgamma-receptors (i.e. FcgammaR I) from normal human peripheral blood lymphocytes and have produced a rabbit antiserum to this protein. Using this antiserum, we have shown that membrane-labile and membrane-stable (i.e. FcgammaR II) Fcgamma-receptors are antigenically distinct and that these two forms of the receptors probably coexist on the same lymphocyte subpopulation. Moreover, it was apparent that lymphocyte FcgammaR Is are distinct from FcgammaRs expressed on other cell types (e.g. monocytes, polymorphs and spermatozoa). Preliminary evidence does suggest, however, that human platelets express an FcgammaR which is antigenically similar to human lymphocyte FcgammaR I.
Subject(s)
Antilymphocyte Serum/immunology , Lymphocytes/immunology , Receptors, Fc/immunology , Animals , Electrophoresis, Polyacrylamide Gel , Humans , Male , Molecular Weight , Platelet Aggregation , Rabbits , Receptors, Fc/isolation & purification , Receptors, IgG , Rosette FormationABSTRACT
In this study, Fc gamma-receptors were isolated from normal human peripheral blood lymphocytes by prolonged incubation at 37 degrees C and purified by affinity chromatography using Sepharose 4B combined with heat-aggregated IgG. These labile Fc gamma R-receptors were shown to be functionally active with an apparent molecular weight of 60 K. Serum Fc gamma-receptor like molecules were also isolated and were shown to be of similar molecular weight. In addition, a high molecular weight (greater than 19S) serum IgG-binding protein was found. The basic sub-unit structure of this molecule was also 60K suggesting that the Fc gamma-receptor may exist in a polymeric or complexed form in normal human serum.
Subject(s)
Lymphocytes/immunology , Receptors, Fc/isolation & purification , Humans , Immunoglobulin G , Molecular Weight , Receptors, IgGABSTRACT
When normal human peripheral blood lymphocytes (PBL) were incubated at 37 degrees with soluble transferrin anti-transferrin (TAT) complexes a significant reduction in the proportion of PBL bearing receptors for the reacted Fc portion of IgG(Fc gamma R) was found. Following incubation of such complex-treated PBL in normal human serum the proportion of Fc gamma R + PBL, as assessed by rosette formation with chicken erythrocytes (E) presensitized with rabbit antibody (A) was found to be significantly increased. Such serum-mediated recovery of Fc gamma R was not affected by pretreating PBL with cycloheximide. Recovery was found to be species restricted, Ca++ dependent and confined to a serum fraction containing molecules of relatively low molecular weight (less than 90,000 Mr). Following absorption with EA the restorative capacity of human serum was lost. These findings suggest that following modulation of human PBL-Fc gamma R by immune complexes, receptors may be restored to the cell surface from a serum pool of 'fluid-phase' Fc gamma R. The origin and biological significance of serum Fc gamma R is not known but it is conceivable that they play an important role in immunoregulation.
Subject(s)
Antigen-Antibody Complex/immunology , Blood , Immunoglobulin G/metabolism , Lymphocytes/immunology , Receptors, Fc/immunology , Humans , Receptors, Fc/analysis , Receptors, IgG , Rosette Formation , Transferrin/immunologyABSTRACT
Following consumption of 1.2 litres of cows' milk by normal human adults there was a rapid fall in the proportion of peripheral blood lymphocytes bearing receptors for the reacted Fc of IgG (Fc gamma-receptors). This phenomenon was transient and apparently confined to the lymphocyte Fc gamma-receptor+ve subpopulation. Similar observations were made in rats but only in those animals pre-exposed to cows' milk suggesting that an immunological mechanism is involved. In man it was found that Fc gamma-receptors could only be re-expressed following incubation of post-milk lymphocytes in normal human serum. It is proposed that rapid in vivo modulation of lymphocyte Fc gamma-receptors occurs following oral antigen (cows' milk) challenge probably mediated by soluble food antigen-antibody complexes. The subsequent recovery of these receptors in vivo and in vitro may be due to the binding of 'fluid-phase' Fc gamma-receptors found in normal human serum.
Subject(s)
Antigens/administration & dosage , Lymphocytes/metabolism , Milk/immunology , Receptors, Fc , Adult , Animals , Antigen-Antibody Complex , Cattle , Humans , Lactoglobulins/immunology , Leukocyte Count , Male , Rats , Rats, Inbred Strains , Receptors, IgG , Receptors, Immunologic , Rosette Formation , Serum Albumin, Bovine/immunology , gamma-Globulins/immunologyABSTRACT
Soluble transferrin-anti-transferrin (TAT) complexes were shown by EA-rosette inhibition assay to block human lymphocyte receptors for the Fc of reacted IgG (Fc gamma) in vitro. These complexes, which provide a convenient and controlled source of Fc gamma receptor blocking material, were found to inhibit EA-rosette formation over a wide range of antigen: antibody ratios. Complexes were detected at both 37 degrees C and 4 degrees C although the range and sensitivity of the assay was markedly increased at 4 degrees C. The inhibitory capacity of TAT complexes was lost on pre-incubation with normal human serum suggesting that only non-complement fixing complexes are detected by EA-rosette inhibition. "False positive" inhibition by antilymphocyte antibodies occurs at 37 degrees C but not at 4 degrees C. Partial automation of the assay was achieved by calibrating a Coulter counter for rosette counting, thus obviating the requirement for tedious and subjective microscopic determinations.
