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Biomedical subjects

H G Kunkel

Publications and source records attributed to H G Kunkel.

At least 19 recordsLinked to original sources
PubMed1979

Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells.

Human T-cell blasts were generated by stimulation with mitogens and antigens. A proportion of these blasts expressed Ia antigens detectable by immunofluorescence with both allo- and hetero-antiserums. The maximal expression of Ia antigens was delayed and usually occurred after the peak of blastogenesis. Among the three mitogens used, pokeweed mitogen (PWM) was most effective in giving a high percentage and intense Ia staining of T-cell blasts. Phytohemagglutinin and concanavalin A blasts gave weaker and lower percentages of Ia staining. Activation by alloantigens and soluble antigens such as tetanus toxoid and purified protein derivative resulted in Ia expression on T cells comparable to PWM stimulation. Depletion of Ia+ cells from freshly isolated T cells with anti-Ia and complement decreased subsequent Ia expression, suggesting that a proportion of Ia+ blasts were derived from Ia-bearing peripheral blood T cells. When the specificities of the Ia antigens on T-cell blasts were examined with alloantiserums, it was evident that the T blasts expressed similar HLA-DR determinants to those on B cells from the same donor; occasional minor differences between stimulated T cells and autologous B-cell lines or fresh B cells were encountered.

Cells, Cultured↗
PubMed1979

Isolation and immunological characterization of a major surface glycoprotein (gp54) preferentially expressed on certain human B cells.

A major membrane glycoprotein with mol wt of approximately 54,000 has been isolated from membrane preparations of B-type lymphoid cell lines. Antiserum prepared against the isolated material specifically precipitated this glycoprotein from membranes labeled by surface radioiodination or by metabolic labeling. This antiserum was shown by complement-mediated cytotoxicity assay, membrane immunofluorescent staining, and by quantitative absorption analysis to react preferentially with certain B-lymphoblastoid cell lines, with a minor population of peripheral blood B lymphocytes, and a major population of tonsillar B lymphocytes. Certain B-cell leukemias also expressed the antigen, whereas others did not. Considerable variability was observed among positive B cells in the intensity of fluorescent staining even among the leukemic cells from a single individual. Although T cells, including T cells, were negative by direct immunofluorescent and cytotoxicity assay, evidence for low levels of the antigen on the cells of T cell lines was obtained. The whole specific antiserum and its F(ab')2 fragments stimulated B lymphocytes to proliferate. This proliferation did not produce differentiation to plasma cells and was T-cell independent. The monovalent Fab fragments had no effect. None of these preparations timulated T cells. The possibility that this antigen, termed gp54, may play some role in B-cell activation is discussed.

Antigens, Surface↗
PubMed1979

Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors.

Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig.

Antibody Formation↗
PubMed1979

Alterations of estrogen metabolism in systemic lupus erythematosus.

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.

Adolescent↗
PubMed1979

Induction of human antibody responses in vitro with emphasis on allogeneic helper factors.

Systems have been developed for the reproducible production of antigen-specific plaque forming cells for both tonsillar and peripheral blood B cells. Allogeneic helper activity was an essential supplement and monocyte removal was important, especially in the peripheral blood situation. Highly active allogeneic helper factors could be obtained from undirectional MLC supernatants which aided the proeuction of antigen-driven plaques. These factors also caused a polyclonal activation of B lymphocytes. A number of clinical applications of the above system were described. A defect in the T cells of patients with chronic lymphocytic leukemia with respect to the generation of helper activities was delineated.

Antibody Formation↗
PubMed1979

Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen.

Peripheral blood mononuclear cells from 46 systemic lupus erythematosus (SLE) patients showed reduced ability to proliferate in vitro in response to the soluble antigen, tetanus toxoid, as compared with 96 normal controls. Special studies of 27 untreated SLE patients also revealed significantly decreased blastogenic responses to tetanus toxoid. In both the total and untreated SLE populations, decreased mean tetanus antibody titers also were found as compared with the control population. However, the reduction in antibody titer and blastogenic response was not strictly parallel. A limited immunization program was initiated in low-responding volunteers from the SLE and normal populations. Three out of four SLE patients did not develop a significant blastogenic response despite increases in anti-tetanus titers after immunization, whereas all normals showed significant increases in both blastogenic and antibody responses. The accumulated evidence indicated that the unresponsiveness was the result of a defect in T-cell function. Monocyte reactivity was demonstrated to be normal, and no evidence was found for the presence of suppressor cells, inhibition by immune complexes, or increased prostaglandins to explain the defect.

Antibodies, Bacterial↗
PubMed1979

Poor mixed lymphocyte reaction stimulatory capacity of leukemic B cells of chronic lymphocytic leukemia patients despite the presence of Ia antigens.

The human Ia-like antigens, selectively expressed on B lymphocytes, are now recognized to be closely associated with, or identical to, the gene products of the major histocompatibility complex responsible for stimulation in the mixed lymphocyte reaction. The leukemic B lymphocytes of patients with chronic lymphocytic leukemia express these antigens very well. In the present study they were readily detected by several techniques utilizing both allo- and heteroantisera. However, the leukemic B cells from most patients were found to be extremely poor stimulating cells in the mixed lymphocyte reaction. This was particularly apparent when comparisons were made on a B-cell basis with isolated normal B lymphocytes. Leukemic cell death, abnormal kinetics of leukemic cell-mediated stimulation, and serum or cellular suppressor factors do not appear to explain these findings. Studies comparing cells from a leukemic patient with those of her HLA identical sibling and results of mixed lymphocyte reactions between normal and leukemic subjects discordant for D-region-associated Ia antigens ruled out genetic explanations for the differences observed. Experiments with normal peripheral blood mononuclear cells depleted of T cells and monocytes exclude the quantitative deficiency of monocytes which is found in the peripheral blood of most leukemic patients as an explanation. The present results with chronic lymphocytic leukemia cells indicate that the mere expression of the Ia-like antigens by cell populations does not render them effective stimulators. The accumulated evidence obtained indicate that abnormalities, particularly of membrane function and metabolism, known to occur in chronic lymphocytic leukemia lymphocytes may be involved in the poor stimulatory capacity of the leukemic B cells.

Animals↗
PubMed1979

Comparison of various tests for Fc receptors on different human lymphocyte sub populations.

Six different immune complex test systems for the detection of IgG Fc receptors were applied to the study of various human lymphocyte populations. The extent of binding varied widely according to the system and the cell type employed. Two systems bound preferentially to a high proportion of B lymphocytes from peripheral blood or tonsils, one of which bound with only a very few T cells. In contrast, four other test systems which bound well with the Fc receptors on T lymphocytes gave weaker reactions with Fc receptors on B cells. The reactivity of Fc receptors on null or third population lymphocytes was similar to that of the Fc-positive T cells. Pronase digestion experiments showed a graded selective loss of reactivity with the different Fc reagents. No one system was optimal for all of the lymphocyte populations, although aggregated IgG exhibited the broadest spectrum of reactivity. A pronounced effect of temperature was evident on the binding reactions, and native IgG showed strong binding at 4 degrees C, particularly to the Fc receptors on T cells.

Antigen-Antibody Complex↗
PubMed1979

T cell helper defect in patients with chronic lymphocytic leukemia.

Purified peripheral blood T lymphocytes from normal donors were shown to help allogeneic tonsillar B cells to differentiate and secrete specific anti-SRBC antibody in vitro in a plaque-forming assay. Utilizing this system, a comparison was made between the allogeneic helper activity generated by the T cells of normal individuals and patients with various disease states. Allogeneic helper activity was absent when T lymphocytes from patients with CLL were used. Conversely, relatively normal allogeneic helper function was provided by T cells of patients with a variety of other disorders studied. Thus, a functional deficiency was identified in CLL patients in the subpopulation of regulatory T cells responsible for providing helper activity in allogeneic interactions.

B-Lymphocytes↗
PubMed1979

Oligoclonal immunoglobulins in subacute sclerosing panencephalitis and multiple sclerosis: a study of idiotypic determinants.

Studies have been made of the idiotypic determinants of subacute sclerosing panencephalitis (SSPE) antibodies using rabbit antisera to serum and spinal fluid fractions. Evidence is presented indicating that serum and cerebrospinal fluid (CSF) anti-measles antibodies, as judged by their idiotypes, differ in their relative concentrations in the two compartments. The results indicate that some of these antibody subpopulations originate within the CNS, while others are made largely or entirely outside. In addition to strong idiotypic specificity, a limited cross-idiotypic specificity relating antibodies from three out of fourteen SSPE patients has been identified. In the course of these studies, measles virus was found to agglutinate red cells coated with antibody fraction to high titres. This system has proved useful in demonstrating the competition between anti-idiotypic antibody and antigen for the combining sites of the measles antibody. Two anti-idiotypic antisera have also been obtained against the spinal fluid IgG of multiple sclerosis (MS) patients. The possible use of these marker reagnets as well as related methodologies in the search for the antigens involved in MS bands is discussed.

Antibody Specificity↗
PubMed1978

Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes.

Successful induction of in vitro differentiation and immunoglobulin synthesis of the leukemic lymphocytes was carried out in two cases of chronic lymphocytic leukemia. Few plasma cells and little specific Ig secretion were detected in the cultures of isolated leukemic B cells in either the presence or the absence of autologous T cells. Up to 30% of the leukemic B cells matured to plasma cells, and a 32-fold increase in specific Ig synthesis was observed when T cells from normal individuals were added to the cultures of these leukemic B cells. In one of the two cases, autologous T cells were able to induce greater than 50% of the leukemic B cells to differentiate further to plasma cells in the presence of pokeweed mitogen. This markedly accelerated in vitro differentiation was only achieved with leukemic cells from cases in which there was evidence of slight differentiation in vivo. No evidence could be obtained for excessive suppressor T cells in these patients. However, a T-cell defect in the generation of allogeneic effect helper factors was identified. This defect may be responsible for the reduced rate of leukemic maturation in vivo.

B-Lymphocytes↗
PubMed1978

Disease associations of the Ia-like human alloantigens. Contrasting patterns in rheumatoid arthritis and systemic lupus erythematosus.

Increasing evidence has been obtained of the special value of Ia-like B-cell alloantisera for demonstrating disease associations with histocompatibility antigens. This was particularly evident for the study of the immunogenetics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), two conditions frequently considered related. The profiles of antigens recognized by the alloantisera in patients from each disease group was distinctive. Two types of alloantisera were obtained that illustrated the divergence between the twod iseases. One type showed a higher than normal incidence in RA but lower than normal in SLE; the other showed a higher incidence in SLE. While these sera were not totally defined, evidence was obtained that the SLE-reactive alloantiserum related to two alleles of the major histocompatibility complex DRw2 and DRw3, while the RA-reactive alloantiserum related to a common specificity shared by cells positive for either DRw4, DRw7, or DRw10. The data indicate that immunogenetic factors are relevant to the development of both RA and SLE, but that these are distinct for each disease.

Antigens, Surface↗
PubMed1978

Ia-bearing T lymphocytes in man. Their identification and role in the generation of allogeneic helper activity.

The presence of Ia-like antigens was demonstrated on a small population (2-6%) of highly purified human circulating T lymphocytes by immunofluorescence with a rabbit anti-Ia serum raised against the isolated bimolecular Ia structure. The Ia+ T lymphocytes have no surface or intracellular immunoglobulins. The expansion of this Ia+ T-cell population was encountered in certain patients. Ia antigens were also found on T blasts grown in long-term cultures with conditioned medium generated by phytohemagglutinin-stimulated lymphocytes. In addition, leukemia blasts which stained for Ia antigens and formed E rosettes were identified in the peripheral blood of two leukemic patients. This evidence further supports the existence of Ia-bearing T cells in man. The Ia+ T-lymphocyte population was shown to contain cells responsible for the generation of allogeneic helper activity. Elimination of Ia+ lymphocytes from a purified T-cell population by the anti-Ia antiserum and complement abolished its ability to help an allogeneic B-cell preparation to generate plaque-forming cells against sheep erythrocytes in vitro in the presence of the antigen.

Antigens, Surface↗
PubMed1978

Inhibition of human erythropoietic colony formation in culture by treatment with Ia antisera.

Incubation with Ia antiserum, followed by complement, markedly inhibited erythroid colonies arising from hematopoietic cells present in the nonadherent low density fractions of normal bone marrow. Both erythropoietin-dependent colonies and bursts were eliminated at dilutions of antiserum equivalent to, or greater than the dilutions required to abolish the granulocyte-macrophage colony formation. The inhibitory effect of the Ia antiserum was abolished by absorption with B but not T cells from lymphoid lines. Available evidence suggested that Ia determinants are expressed on the erythropoietin-sensitive progenitors of the erythroid series in precise analogy to their sequence of expression on the granulocyte lineage. In both lineages, as shown previously, the Ia determinants become undetectable during subsequent stages of differentiation.

Antigen-Antibody Reactions↗