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Biomedical subjects

R S Geha

Publications and source records attributed to R S Geha.

At least 271 records · Page 15Linked to original sources
PubMed1981

Enumeration of T cell subsets in atopic dermatitis using monoclonal antibodies.

Peripheral blood lymphocytes from 22 patients with atopic dermatitis, 17 age-matched healthy controls, 10 patients with other skin diseases, and 14 patients with either asthma or allergic rhinitis were characterized by reactivity with monoclonal antibodies to the surface antigens of helper-inducer (T4) and suppressor-cytotoxic (T8) T cell subsets and to a common T cell antigen (T3). In contrast to healthy controls and controls with other skin diseases or respiratory allergic disease, patients with atopic dermatitis had a reduced percentage of T3-positive (T3+)cells (p less than 0.01) and T8-positive (T8+) cells (p less than 0.001) but not of T4-positive cells (T4+)op less than 0.05). A selective increase in the ratio of T4+ cells over T8+ cells was observed in 17 of 22 patients with atopic dermatitis but not in any of the controls. Thus there is a loss of circulating suppressor-cytoxic T cells in the majority of patients with active atopic dermatitis.

Adolescent↗
PubMed1981

Deficiency of suppressor T cells in the hyperimmunoglobulin E syndrome.

The status of suppressor T cells (Ts) was assessed in seven children with the hyper IgE syndrome (recurrent staphylococcal infections, eczematous skin rash, and elevated serum IgE) to determine whether a deficiency in Ts is associated with increased IgE synthesis. When circulating T cells and their subsets were enumerated with the aid of monoclonal antibodies that identify T cells (T3), helper/inducer T cells (T4), and suppressor/cytotoxic T cells (T8), there was a selective deficiency of T3+ cells (51.7+/-11.2% vs. 66+/-5% for normal controls) and of T8+ cells (7.5+/-4.4% vs. 22+/-4% for normal controls) but not of T4+ cells (36.5+/-7.5% vs. 37+/-3% for normal controls). Suppressor T cell function was assessed by examining the ability of mononuclear cells incubated for 48 h with concanavalin A to suppress the proliferation of fresh autologous mononuclear cells in response to the mitogens phytohemagglutinin and pokeweed mitogen. All seven patients were severely deficient in concanavalin A-inducible suppressor cells. In vitro de novo synthesis of IgE in 6-d cultures of peripheral blood lymphocytes was measured in four patients by a solid-phase radioimmunoassay. Mononuclear cells from all four patients synthesized spontaneously increased quantities of IgE in vitro (4,950+/-3,760 pg/10(6) cells vs. 250+/-215 pg/10(6) cells for eight normal controls). IgE synthesis was suppressed by the addition of parental T cells to the culture. Elimination of the T8+ subset, but not of the T4+ subset, by complement-dependent lysis resulted in the loss of the capacity of parental T cells to suppress IgE synthesis. These results suggest that a deficiency of Ts underlies the elevated IgE levels observed in the hyper IgE syndrome.

Adult↗
PubMed1981

Macrophage T cell interaction in man: binding of antigen-specific human proliferating and helper T cells to antigen-pulsed macrophages.

Adsorption of T cells over monolayers of autologous, but not allogeneic, macrophages (M phi) pulsed with tetanus toxoid (TT) antigen resulted in the specific depletion of the capacity of the T cells to proliferate and to release T cell helper factor in response to stimulation, with TT antigen. T cells that bound to the TT-pulsed M phi monolayers were specifically enriched in their capacity to proliferate in response to TT. Turkey antiserum to the human B cell glycoprotein p 29,34, but not turkey antiserum to human beta 2 microglobulin, inhibited the binding of TT-reactive T cells to TT-pulsed M phi. This inhibition resulted from the binding of the anti-p 29,34 antiserum to DR determinants expressed on the surface of the M phi. Immunosorbent purified IgG anti-TT, added in great excess, did not inhibit the binding of TT-reactive T cells to TT-pulsed M phi monolayers. Soluble TT antigen and rabbit antiidiotypic IgG, directed against IgG F(ab')2 anti-TT obtained from the cell donor, minimally inhibited the binding of TT-reactive T cells to TT pulsed M phi monolayers. M phi pulsed with urea-denatured TT, which contained less than 1% native TT, depleted T cell reactivity to TT to an extent almost equivalent to that achieved by M phi pulsed with native TT. These results indicate that human antigen-reactive T cells bind to the DR determinants of M phi pulsed with antigen and that the immunogenic moiety of antigen recognized by the majority of antigen reactive human T cells may differ from native antigen.

Adsorption↗
PubMed1980

Increased serum immunoglobulin E levels following allogeneic bone marrow transplantation.

IgE levels were determined before and serially after allogeneic bone marrow transplantation (BMT) in 12 patients. Six patients had aplastic anemia, four leukemia, and one each Wiskott-Aldrich syndrome and infantile agranulocytosis. IgE levels increased sharply (7- to 2,000-fold) in 10 of the 12 as early as 14 days after BMT. They all returned to baseline levels by 60 days. In six of these patients, the rise accompanied clinical and biochemical evidence of acute graft-versus-host disease (GVHD). All of the patients who received rabbit antihuman thymocytic serum (ATS) in preparation for transplantation and were tested for IgE antirabbit serum antibody by radioallergosorbent test (RAST) (n = 6) developed a strongly positive RAST which paralleled their total IgE levels. These high IgE levels detected during the period of acute GVHD may be a manifestation of a transient lack of suppressor T cell activity.

Adolescent↗
PubMed1980

Regulation of monoclonal immunoglobulin G synthesis by antiidiotypic antibody in a patient with hypogammaglobulinemia.

The regulation of in vitro antibody synthesis by antiidiotypic antibodies was studied in a child with hypogammaglobulinemia and a serum immunoglobulin (Ig)G1 kappa M component. A rabbit antiserum was raised against the purified M component and was rendered idiotype specific by extensive absorption with Cohn fraction II and with IgG derived from the patient's parents. Hemagglutination-inhibition studies demonstrated that less than 1 in 300,000 molecules of pooled human IgG carried M component-related idiotypic determinants. 12% of the patient's B cells, but none of her T cells, expressed idiotypic determinants on their surface. Spontaneous de novo synthesis of the M component by the patient's peripheral blood lymphocytes was demonstrated in vitro and was shown to proceed independently of the polyclonal activator pokeweed mitogen. Antiidiotypic rabbit IgG, but not its F(ab')2, fragments, profoundly inhibited the synthesis of M component by the patient's peripheral blood lymphocytes. We concluded that antiidiotypic antibodies may play a role in the regulation of antibody synthesis in man.

Agammaglobulinemia↗
PubMed1980

Hapten-specific T-cell unresponsiveness induced bybenzylpenicilloyl autologous gamma globulin conjugates in human lymphocyes in vitro.

The aim of these studies was to determine whether unresponsiveness to the main determinant of penicillin, benzylpenicilloyl, can be induced in human peripheral lymphocytes in vitro by conjugates of benzylpenicilloyl (BPO) autologous gamma globulin (HGG). Initially it was shown that conjugates of BPO-keyhole limpet hemocyanin (KLH) elicited lymphocyte proliferation in the peripheral blood lymphocytes of six out of nine adult individuals in vitro. In contrast, conjugates of dinitrophenylated KLH and of BPO-HGG and the carriers HGG and KLH alone failed to do so. Similarly, release of the non-specific helper factor, lymphocyte mitogenic factor (LMF) occurred only after BPO-KLH stimulation. LMF activity was measured by B-cell proliferation and incorporation of radioactive amino acids into secreted immunoglobulin. Treatment with BPO-HGG for 24 h in vitro inhibited BPO-KLH-induced lymphocyte proliferation and LMF release. Treatment with either HGG, dinitrophenylated HGG, BPO-KLH, or BPO-human serum albumin failed to abrogate T-cell lymphocyte proliferation of human lymphocytes in vitro. The antigen specificity of the reduced immunologic responsiveness was further demonstrated by the observation that lymphocytes treated with BPO-HGG for 24 h in vitro responded normally to tetanus toxoid antigen.The data suggest that conjugates of BPO-HGG induce hapten-specific helper T-cell unresponsiveness in vitro.

Haptens↗
PubMed1980

The immune system development and function.

The immune system in its four components T cells, B cells, complement and phagocytes is vital for the defense of the organism against foreign substances or antigens. Elimination of an antigen involves the interaction of the four complements of the immune system with antigen and with each other. The final common pathway is the breakdown of the antigen by the intracellular machinery of the phagocytic cell. The maintenance of the self depends on the integrity of the immune system. Whenever this integrity is breached (by aging, congenital immune deficiency, cytotoxic drugs, irradiation, infiltrative disease...) the organism becomes prone to uncontrolled invasion by antigens (viruses, bacteria, fungi, neoplasms) and its survival is threatened.

Complement System Proteins↗
PubMed1980

The immune system: primary immune deficiency diseases.

Table 1 summarizes the major IDD and the methods used for their diagnosis and treatment. The clue to the diagnosis of IDD remains a high index of suspicion when one encounters a child or an adult with recurrent infections. IDD must be relatively common in Lebanon because of the high rate of interfamily marriages. With a heightened awareness and few easily available laboratory methods (underlined in table 1) the primary physician should be able to make the diagnosis of most of these diseases.

Complement System Proteins↗
PubMed1979

Abnormalities of immunoregulatory T cells in disorders of immune function.

We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.

Adolescent↗
PubMed1979

Transient hypogammaglobulinemia, elevated immunoglobulin E levels, and food allergy.

Four infants presented with the combination of food allergy, transient hypogammaglobulinemia (THI), and elevated serum IgE levels. Food allergy was documented by history, positive skin tests for immediate hypersensitivity, radioallergosorbent test, histamine release studies, and lymphocyte transformation in response to food allergens. THI was probably secondary to decreased production since there was no evidence of protein loss from the gastrointestinal tract. Immunologic studies revealed normal B cell number and function in vitro. T cell number and proliferative response to mitogens and antigens were normal but T cells were deficient in their ability to generate helper factors necessary for B cell maturation into immunoglobulin secretory cells. The THI and the deficient production of T cell--helper factor resolved after the age of 20 to 24 mo. A defect in immunoregulation may be responsible for the immunologic abnormalities observed in these patients and their propensity to develop IgE antibodies to food allergens.

Agammaglobulinemia↗
PubMed1979

Effect of anti-HLA antisera on macrophage-T-cell interactions.

Human T lymphocytes were shown to proliferate in response to tetanus toxoid antigen only in the presence of macrophages. This response was inhibited by anti-DRw but not by anti-HLA (A and B loci) antisera added to the cultures and by pretreatment of macrophages but not of T cells with anti-DRw antisera and complement. Macrophages pulsed for 18 hr with antigen and then washed were capable of triggering T-cell proliferation. Addition of anti-DRw but not anti-HLA (A and B loci) antisera during the pulse period inhibited the macrophages' ability to trigger T-cell proliferation. The data obtained indicate that human T cells recognize and proliferate in response to antigen presented by the macrophages in association with Ia-like antigens.

Antibody Formation↗
PubMed1979

Hyper immunoglobulin M immunodeficiency. (Dysgammaglobulinemia). Presence of immunoglobulin M-secreting plasmacytoid cells in peripheral blood and failure of immunoglobulin M-immunoglobulin G switch in B-cell differentiation.

The peripheral blood lymphocytes of nine patients with hyper immunoglobulin (Ig)M immunodeficiency were studied in an attempt to define the cellular basis of this disorder. B cells were normal in number but qualitatively abnormal in all patients. Approximately one-half of the B cell consisted of small lymphocytes (7-9 mum in diameter) bearing surface IgM and IgD, as well as C3 receptors. These cells were driven to secrete IgM but not IgG after in vitro stimulation by pokeweed mitogen. In the blood there were also large lymphocytes (10-14 mum in diameter) that possessed surface as well as intracytoplasmic IgM but lacked C3 receptors. These cells spontaneously secreted large amounts of IgM in vitro and on electron microscopy were found to be rich in rough endoplasmic reticulum. Such a subpopulation of lymphoid cells was not detected in normal peripheral blood and was unique for all patients with hyper IgM immunodeficiency studied.T cells from all patients were normal in number and in function both in vivo and in vitro and were able to generate adequate T-cell help to support IgG synthesis by normal B cells. No evidence was obtained for T cells capable of suppressing normal IgG synthesis in any of the patients after coculture with normal peripheral blood lymphocytes. The defect in hyper IgM immunodeficiency is intrinsic to B cells, which fail to switch from IgM to IgG synthesis.

Adult↗