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Biomedical subjects

H M Gebel

Publications and source records attributed to H M Gebel.

At least 55 records · Page 3Linked to original sources

Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody.

Previously we have demonstrated that islets of Langerhans treated with donor-specific anti-Ia serum and complement survive when transplanted across the major histocompatibility complex of the mouse. In this study, using immunofluorescence, we demonstrate two morphologically distinct populations of Ia-positive cells scattered within the Ia-negative islet tissue. A large irregularly shaped Ia-positive subset of cells were identified as dendritic cells by using the 33D1 antibody specific for a mouse dendritic cell antigen. The other small, round Ia-positive subset was 33D1 negative. Islets pretreated with anti-dendritic cell antibody and complement prior to transplantation survived in their histoincompatible recipients for greater than 200 days. Rejection of stable islet allografts promptly occurred when transplant recipients were challenged with 1 X 10(5) donor dendritic cells 60 days after transplantation. These results demonstrate an important in vivo role for donor dendritic cells in the stimulation of allograft rejection.

Animals↗

Antibodies directed against HLA-DR gene products exhibit the CYNAP phenomenon.

Two well characterized Eighth International Workshop sera, 8w1090 and 8w112 , described to have anti-DR3 and anti-DR5 activity, respectively, were tested by standard and antiglobulin augmented (AHG) complement dependent cytotoxicity (CDC) assays with 21 target cells. We demonstrate that both sera, in fact, have only one antibody (most likely anti-MT2), but have different CYNAP patterns. These observations are discussed with regard to a more complete analysis of antisera that detect gene products of the HLA-DR region.

Antibodies↗

Thymectomy-induced decrease in T gamma cells and OKT8+ cells in multiple sclerosis.

Studies were performed on lymphocytes from patients with multiple sclerosis before and after thymectomy (group I) and before and after thymectomy and azathioprine therapy (group II), and from matched control patients with multiple sclerosis, control patients with other neurological diseases, and healthy control subjects. Following treatment the percentage of T gamma cells in both group I and group II patients decreased from above the mean normal control levels to below this level; OKT8+ cell numbers in group I became lower than in any of the control groups; the percentage of concanavalin A-induced suppressor activity, which was initially normal, fell in group II and suggestively but not significantly in group I; and total blood lymphocytes in group I decreased from normal to below control levels. Other tests showed no significant changes with therapy. No significant difference in changes in clinical status were observed after one year in the treated patients compared with matched controls.

Adult↗

Detection of two distinct public specificities on HLA-A28 bearing lymphocytes.

We have used the antiglobulin augmented cytotoxicity assay and platelet absorption-elution techniques to investigate crossreactivity among certain antigens coded by the HLA-A locus. These serologic and absorption studies demonstrated two supertypic determinants, distinct from private determinants, associated with HLA-A locus gene products. One determinant was present on HLA-A2, Aw23, Aw24, and A28 bearing lymphocytes; the other was found on HLA-A28, Aw33, Aw34, and A26 bearing lymphocytes. The second determinant was not associated with HLA-A25. Both supertypic determinants are associated with HLA-A28.

Antibody Specificity↗

In vitro response of human T cells to Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a gram-negative bacillus that is a major cause of morbidity and mortality in immunosuppressed patients, burn patients, and patients with cystic fibrosis. Although immunity to these bacteria has been associated with serum antibody, more recent evidence suggests that T-cell-mediated immunity may also be important. To evaluate human T-cell responsiveness to these bacteria, the optimal conditions were determined for in vitro proliferation of human peripheral blood lymphocytes and T-lymphocytes to Fisher-Devlin immunotype 1 P. aeruginosa. The proliferative response of normal adult peripheral blood lymphocytes to heat-killed P. aeruginosa was studied in 34 subjects (range, 7,600 to 111,500 net cpm). Analysis of cell subpopulations indicated that T-lymphocytes are the major proliferating cells and that this response is enhanced by the presence of adherent cells. Data from fetal cord lymphocyte responses suggest that the proliferation seen in normal adult lymphocytes is induced by antigenic and not mitogenic stimulation.

Age Factors↗

In vitro immunization to KLH. II. Limiting dilution analysis of antigen-reactive cells in primary and secondary culture.

Limiting dilution analysis was used to estimate the frequency of human peripheral blood T lymphocytes that proliferate in response to in vitro immunization with keyhole limpet hemocyanin (KLH). Antigen-reactive cells (ARC) were estimated 9 days after primary immunization with KLH. The ARC frequency of lymphocytes from 12 subjects ranged from 1:23,800 to 1:52,631. Lymphocytes from five of these subjects were also primed for 12 days with KLH, rechallenged in secondary culture with fresh adherent cells and KLH, and assayed 4 days later. The ARC frequency increased to 1:1,123 to 1:7,247, indicating that T cell clones responsive to KLH had expanded during primary culture. In addition, we observed that the proliferative response of lymphocytes from 5 of the 12 subjects were inhibited at high cell concentrations. Depletion of OKT8+ T cells before culturing with KLH however did not alter the inhibitory effect of high concentrations of T cells.

Cells, Cultured↗

Cutaneous anergy and marrow suppression as complications of gastroplasty for morbid obesity.

Although serious morbidity from gastric restriction for morbid obesity is rare, outflow tract dilation after gastroplasty has become a well-recognized complication, and reoperation to decrease outflow tract size has become increasingly common. We report the case of a patient who developed outflow tract obstruction with subsequent malnutrition, recurrent infections, and marrow suppression. Extensive immunologic evaluation revealed impaired cutaneous reactivity to a battery of recall antigens. Other in vitro T cell functions, B cell functions, neutrophil respiration, and quantification of complements were within normal limits. The patient's immunodeficiency was attributed to protein-calorie malnutrition and was corrected with total parenteral nutrition. Recovery of immune function with renutriture was demonstrated, and coincident resolution of infection and marrow suppression also occurred. Because of the reversibility of the immunologic abnormality with appropriate nutritional therapy, it is important to consider and treat malnourishment in connection with any operation in which oral intake is severely limited.

Adult↗

Demonstration of a third structurally distinct human Ia beta chain by two-dimensional gel electrophoresis.

Previous studies have indicated that HLA-DR homozygous cell lines express two Ia alpha and Ia beta chains that combine to form at least two Ia molecules. This report demonstrates by two-dimensional gel electrophoresis the existence of a third structurally distinct human Ia beta chain on DR2 and DR5 cell lines. This suggests that at least five separate genes control the expression of Ia molecules on HLA-DR homozygous cell lines.

B-Lymphocytes↗

Antigenic specificity of antibody reactive in the antiglobulin-augmented lymphocytotoxicity test.

The addition of an antihuman immunoglobulin (AHG) reagent to the basic complement-dependent cytotoxicity (CDC) test markedly increases the frequency of lymphocyte-reactive antibodies in many alloantisera. The extra reactivity has been previously identified as associated with alloantigens coded by the HLA complex, but definitive evidence establishing the antigenic specificity of the antibodies reactive by AHG-CDC has been lacking. We determined the nature and specificity of AHG-reactive alloantibodies through parallel testing (CDC +/- AHG) of a large battery of HLA alloantisera against panel cells composed of unrelated individuals and genotypic HLA-identical sibling pairs, and by means of differential platelet absorption and elution of alloantibody. We conclude that the AHG-CDC procedure, relative to "standard" CDC, detects subthreshold levels of alloantibody with specificity for the HLA-A, B, and C locus alloantigens. Most importantly, the AHGG-CDC technique consistently converts cytotoxicity-negative absorption-positive (CYNAP) HLA alloantibody to direct cytotoxic antibody, thus providing a more accurate assessment of the complete specificity of antibodies in complex alloantisera and patients' sera without having to resort to more cumbersome binding assays. These data should be of assistance in improving the characterization of HLA alloantisera used for serological and biochemical studies of the HLA molecules and in delineating the specificity of AHG-CDC antibody in clinical allotransplantation and single-donor platelet transfusion.

Absorption↗

Molecular relationships of the human B cell alloantigens, MT2, MB3, MT4, and DR5.

The human class II, HLA-linked, B cell alloantigens include the HLA-DR, MB, MT, and Te determinants. Interest in the molecular relationships of these antigens has recently intensified because of their homology to the murine Ia antigens and their possible importance in disease predisposition and transplantation. We have used alloantisera with carefully defined immunochemical as well as serologic specificity, and two immunochemical techniques, sequential immunoprecipitation with analysis by SDS-PAGE and two-dimensional gel electrophoresis, to explore the molecular relationships of the MT2, MB3, MT4, and HLA-DR5 antigenic determinants. The data presented here indicate that 1) all class II molecules that bear the DR5 antigenic determinant also bear the MT2 antigenic determinant; (2) the homozygous DR5 cell line, Swei, expresses at least two structurally distinct class II molecules, both of which bear MT2: one bears the MT2, MB3, and MT4 antigenic determinants, and the second bears the MT2, but not the MB3 or MT4 antigenic determinant; and (3) the DR5 determinant is located on at least one and possibly both of these distinct class II molecules.

Absorption↗

Delayed hypersensitivity in Alzheimer's disease following BCG immunostimulation.

Forty-four patients with Alzheimer's disease were evaluated for delayed hypersensitivity responses using five ubiquitous antigens. Compared with a nondemented age-matched population, these patients evidenced a large number of deficient responses, especially in the zero-response group. Twenty-three patients were randomly selected for immunostimulation using BCG vaccine. The skin tests were repeated 2 weeks after a series of four weekly intradermal injections of BCG. Only 2 of 13 nonresponsive patients failed to convert at least one negative result into a positive response, and seven became normal.

Aged↗

Expansion of Fc receptor-bearing T lymphocytes in patients with immunoglobulin G and immunoglobulin A myeloma.

Lymphocytes obtained from the blood of normal individuals and six patients with newly diagnosed multiple myeloma were separated into T and non-T cell populations by rosette-formation with sheep erythrocytes, and were then assayed for the presence of surface membrane Fc receptors. When compared with normal individuals, four patients with IgG myeloma had a three- to fourfold increase in T cells with IgG receptors (T gamma cells) and two patients with IgA myeloma had a two- to threefold increase in T cells with IgA receptors (T alpha cells). Patients with IgG or IgA myeloma had normal numbers of non-T lymphocytes with surface receptors for IgG and IgA, respectively. The finding that human myeloma is accompanied by elevated numbers of T cells with Fc receptors for the heavy chain class of the myeloma protein: (1) may account for the apparent "monoclonal" lymphocyte population in patients with myeloma; (b) extends to humans similar observations made in mice with secretory plasmacytomas; and (c) is of interest because T cells with Fc receptors are immunoregulatory lymphocytes.

Cell Count↗

Functional characteristics of TG and TnonG cells in a three party MLR.

Human peripheral blood T lymphocytes were separated into highly purified Fc gamma receptor-positive (TG) and negative (TnonG) populations. These subgroups were compared with unseparated T cells for their ability to proliferate in response to concanavalin A or allogeneic cells, and to suppress a mixed leukocyte culture reaction (MLR). TG cells fail to vigorously proliferate in response to Con A or irradiated allogeneic cells. Moreover, the response of TnonG populations to Con A and allogeneic cells is enhanced compared with unseparated T cells, suggesting active suppression by TG cells. The suppressive effects of TG cells was confirmed in a 3-party MLR. In contrast, TnonG cells failed to suppress the MLR. However, Con A-activated TnonG cells did suppress the MLR and were as effective as TG cells.

Concanavalin A↗