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The role of T lymphocytes in patients with food-sensitive atopic dermatitis

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hens egg or cows milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hens egg or cows milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hens egg were significantly higher than those of healthy children and patients sensitive to hens egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.

Suppression of immunoglobulin production of lymphocytes by intravenous immunoglobulin

The proliferative responses and the immunoglobulin production of peripheral blood mononuclear cells to pokeweed mitogen were dose-dependently suppressed by sulfonated intravenous immunoglobulin (IVIG), polyethylene glycol-treated IVIG, pH 4-treated IVIG, or human γ-globulin, but they were not or only slightly suppressed by human serum albumin or pepsin-treated IVIG. Moreover, the suppression of immunoglobulin production by sulfonated IVIG, polyethylene glycol-treated IVIG, or pH 4-treated IVIG was seen in the cases in which B cells preincubated with IVIGs were cocultured with T cells and monocytes preincubated with or without IVIGs and in the cases in which monocytes preincubated with IVIGs were cocultured with T cells and B cells preincubated with or without IVIGs. However, in the cases in which only T cells were preincubated with IVIGs, immunoglobulin production was not suppressed. The suppression of the monocyte function by IVIGs tended to be less than the suppression of the B-cell function by IVIGs. Moreover, the suppression by IVIGs was blocked by antihuman IgG Fc. Our results suggest that IVIGs suppress the immunoglobulin production of lymphocytes through suppression of the B-cell function and the antigen presenting-cell function by attachment of IVIGs to Fc receptors of B-cell membranes and antigen presenting-cell membranes.

IGG2 DEFICIENCY ASSOCIATED WITH DEFECTS IN PRODUCTION OF INTERFERON-GAMMA : COMPARISON WITH COMMON VARIABLE IMMUNODEFICIENCY

We report a novel mechanism of IgG2 deficiency. Several investigators have reported patients with IgG subclass deficiencies due to homozygous deletion of immunoglobulin heavy chain constant region genes. However, it is unclear what mechanism is responsible for IgG subclass deficiency in cases where no gene deletions have been detected and which are accompanied by recurrent infections due to aberrant immunoregulation. In the present study, we have focused our attention on production by peripheral blood mononuclear cells (PBMCs) of interferon‐gamma (IFN‐γ), which is known to induce IgG2 expression. PBMCs from four patients with IgG2 deficiency and their families were studied. Mitogen‐induced IFN‐γ production by PBMCs was decreased in all of the patients, although the proliferative responses of PBMCs and the percentages of CD3, CD4, and CD8 T cell subsets were not decreased. IgG2 production by PBMCs was restored upon addition of IFN‐γ and mitogen to the PBMCs of the patients with IgG2 deficiency though it was not restored in the patients with common variable immunodeficiency. We conclude that defects in production of IFN‐γ play an important role in IgG2 deficiency.

Defective Calcium-Dependent Signal Transduction in T Lymphocytes of Ataxia-Telangiectasia

T‐cell functions of two patients with ataxia‐telangiectasia were investigated. Patients with ataxia‐telangiectasia had reduced percentages of circulating CD3+ cells and CD4+ cells, although neither patient had a reduced percentage of circulating CD8+ cells. The proliferative responses and interleukin‐2 production of peripheral blood mononuclear cells to T‐cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4+ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4+ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca2+‐dependent signal transduction through the CD3 complex of the surface in T cells of ataxia‐telangiectasia.

Long‐term study of the immunodeficiency of Bloom's syndrome

The immune state was evaluated over a 10‐year period in two individuals with Blooms syndrome. In both patients, serum concentrations of IgM were markedly low. Mildly decreased serum concentrations of IgG and IgA increased significantly with age, whereas the IgM levels remained low. From assessments of B‐cell and T‐cell functions in pokeweed mitogen‐induced immunoglobulin production, the IgM deficiencies were thought to result from B‐cell dysfunction. T‐cell function appeared intact. Moreover, although the percentages of surface IgM‐bearing cells were not reduced, the numbers of IgM‐secreting cells were reduced. These findings suggest that the IgM deficiency is due to an abnormality in the maturation of surface IgM‐bearing B cells into IgM‐secreting cells.

Accelerated expression of secreted α-chain gene in anaphylactoid purpura

The mechanisms of the elevation of serum IgA levels in anaphylactoid purpura were investigated. Serum IgA levels were significantly elevated within 2 weeks (5 to 14 days for all 12 patients) after onset in patients with anaphylactoid purpura. Serum IgM and IgG were not elevated. Although the percentages of surface IgA-bearing cells were not increased in the patients, the numbers of IgA-secreting cells within 2 weeks after onset in the patients with anaphylactoid purpura were significantly higher than those of controls. In northern blot analysis on lymphocytes, the secreted α (αs)-chain gene was well expressed compared with the membrane-bound α (αm)-chain gene, within 2 weeks after the onset of anaphylactoid purpura. Therefore, stimulation by a certain agent or a certain immune response may accelerate expression of the αs-chain gene in anaphylactoid purpura.

Insulin-dependent diabetes developed in a young man with Bloom's syndrome

Sirs, Bloom’s syndrome (Bloom 1954) is a rare autosomal recessive disorder characterized by growth deficiency, unusual facies, sunsensitive facial erythema, immunodeficiency and a predisposition to various types of cancer. Increased sister chromatid exchanges (Chaganti et al. 1974), chromosome breakage and DNA ligase I deficiency (Chan et al. 1987, Willis et a]. 1987) are the typical findings in cultures of lymphocytes and fibroblasts. Diabetes mellitus develops with unusual frequency in Bloom’s syndrome. It is usually non-insulin-dependent diabetes (German & Passarge 1989). In CZinical Genetics (1990) 38: 387-390, we reported on a 21-year-old Japanese male patient (Bloom’s Syndrome Registry 96HiOk) with Bloom’s syndrome who had exhibited impaired glucose tolerance in the initial oral glucose tolerance test and had developed the pattern of non-insulin-dependent diabetes by the second oral glucose

Chediak‐Higashi syndrome: report of a case with an ovarian tumor

Bakker, E., C. Van Broeckhoven, E. J. Bonten, M. J. van de Vooren, H. Veenema, W. Van Hul, G. J. B. Van Ommen, A. Vandeberge & P. L. Pearson (1987). Gennljne mosaicism and Duchenne muscular dystrophy mutations. Nature 329, 554556. Bakker, E., H. Veenema, J. T. Den Dunnen, C. Van Broekhoven, P. M. Grootscholten, E. J. Bonten, G. J. B. Van Ommen & P. L. Peanon (1989). Germinal mosaicism increases the ncurrence risk for “new”Duchenne muscular dystrophy mutations. J. Med. Genet. 26, 553-559. Chamberlain, J. S.. R. A. Gibbs, J. E. Ranier, P. N. Nguyen & C. T. Caskey (1988). Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acidr Res 16. 11 141-1 1156. Darras, B. T. & U. Francke (1987). A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male. Nature 329, 556-558. Darras, B. T., P. Blattner. J. F. Harper, A. J. Spiro, S. Alter & U. Francke (1988). Intragenic deletions in 21 Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) families studied with the Dystrophin cDNA: location of breakpoints on Hind111 and BglII exoncontaining fragment maps, meiotic and mitotic origin of the mutations. Am. J. Hum. Genet. 43,620429. Hall, J. (1988). Review and hypotheses. Somatic mosaicism: observations related to clinical genetics. Am. J. Hum. Genet. 43, 355-363.

Common variable immunodeficiency with increased surface IgM-positive double-bearing B cells.

We report a case of common variable immunodeficiency (CVI) that shows low levels of IgG and IgA, but a normal quantitative or qualitalive level of IgM. T‐cell functions were not disturbed. Increased numbers of surface IgM (sIgM) and sIgD, sIgM and sIgA, sIgM and sIgA double bearing B cells were observed as compared with a control. No IgG and IgA induction upon stimulation with Staphylococcus aureus Cowan I (SAC)and recombinant interleukin‐2(rIL‐2), or pokeweed mitogen (PWM) and rIL‐4 or rIL‐6 was observed, although there was proliferation. Although; μ mRNA was expressed as much as in a healthy control, transcription of γ mRNA and α mRNA was very low. Furthermore, no enhanced effects of γ mRNA and α mRNA were recognized upon stimulation with rIL‐4 and rIL‐6. These results suggest that the patients B cells might be detective at the switching process from μ, μ and δ, μ and γ to γ or μ and α to α.

Expression of Secreted Immunoglobulin Heavy Chain Genes and Immunoglobulin‐Secreting Cells in Human Lymphocytes

The numbers of immunoglobulin‐secreting cells in peripheral blood mononuclear cells and the expression of mRNA for secreted type of immunoglobulin heavy chains were investigated in healthy children, compared with the percentages of surface immunoglobulin‐bearing cells and the expression of mRNA for membrane‐bound type of immunoglobulin heavy chains, respectively. Although a difference between expression of μs mRNA and μm mRNA was unclear, μmRNA was well transcribed. The expression of γs mRNA or αs mRNA was markedly higher than that of γm mRNA or αm mRNA. However, although the detection methods could be of different sensitivities, the percentage of IgM‐, IgG‐, or IgA‐secreting cells was markedly low, compared with the percentage of surface IgM‐, IgG‐, or IgA‐bearing cells, respectively. Therefore, additional regulation of the pattern of the immunoglobulin gene expression may be exerted at the translational and post‐translational stages.