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Biomedical subjects

W Strober

Publications and source records attributed to W Strober.

At least 199 records · Page 11Linked to original sources
PubMed1981

Covert suppressor T cells in Crohn's disease.

To determine whether patients with Crohn's disease have a defect in immune regulation, suppressor T-cell activity was assessed in 16 patients with mild or inactive Crohn's disease and was compared with that of an equal number of randomly selected normal controls. Pokeweed mitogen-stimulated cultures of peripheral blood lymphocytes from patients synthesized as much IgM as those from normal controls. In addition, cocultures of patient and normal peripheral blood lymphocytes did not result in either suppression or enhancement of immunoglobulin M synthesis. In contrast to these results with cultures of peripheral blood lymphocytes, cultures containing optimal ratios of purified B cells and T cells from patients synthesized significantly less immunoglobulin M (p less than 0.005) than those from normals; in fact, the latter cultures from 6 patients synthesized no detectable immunoglobulin M. Detailed studies of cells from these patients indicated that a suppressor T cell was revealed in vitro during the cell-purification procedure. Finally, in those patients in whom it could be measured, radiation-sensitive suppressor T-cell activity was found to be normal. We conclude that there is no deficiency of suppressor T cells regulating antibody synthesis in patients with Crohn's disease; on the contrary, at least one-half of these patients have suppressor T cells that markedly inhibit the synthesis of immunoglobulin M, but which are revealed only after purification of the T cells.

Adult↗
PubMed1981

Immunoregulatory function of T cells activated in the autologous mixed lymphocyte reaction.

This study was undertaken to define the functional properties of T cells stimulated in the autologous mixed lymphocyte reaction (MLR) by purified B cells or macrophages. In preliminary experiments, it was found that T cells that had been cultured with autologous non-T cells inhibited pokeweed mitogen- (PWM) stimulated immunoglobulin synthesis by autologous B cells. In addition, the T cell-mediated suppression was eliminated by x-irradiation and hydrocortisone treatment, was mediated by a mechanism that occurred early in the PWM-stimulated cultures, and did not involve killing of mature immunoglobulin-secreting cells. T cells were then cultured with either autologous B cells or macrophages in order to determine whether such autoreactive T cells had a similar capacity to regulate PWM-induced immunoglobulin synthesis. Although T cell populations stimulated either by B cells or by macrophages suppressed proliferative responses and immunoglobulin synthesis, both these populations of autoreactive T cells provided help for immunoglobulin synthesis that was not significantly different from that provided by fresh T cells. These results suggest that the predominant functional consequence of activation of T cells in the autologous MLR is the generation of suppressor T cells capable of inhibiting immunoglobulin synthesis. Thus, the autologous MLR may represent a negative feedback mechanism for the regulation of the immune response.

B-Lymphocytes↗
PubMed1981

Specific anti-influenza virus antibody production in vitro by human peripheral blood mononuclear cells.

Cultures of human peripheral blood mononuclear cells stimulated in vitro with influenza virus were found to produce anti-influenza virus antibody. An enzyme-linked immunosorbent assay was used to measure cumulative antibody secretion into culture supernatants. Optimal antibody production was obtained with 2 x 10(6) peripheral blood mononuclear cells cultured in flat-bottomed wells for 12 days in 2 ml of RPMI 1640 medium supplemented with 10% fetal calf serum, antibiotics, and 4 mM L-glutamine. Antibody could be detected in cultures stimulated with live A/Hong Kong/68 (H3N2), purified formalin-inactivated A/Aichi/68 (H3N2), or live B/Hong Kong/68 influenza virus. Antibody of both IgG and IgM isotypes was produced. Under optimum conditions, the secreted IgG antibody was found to be directed preferentially at antigens on the stimulating virus. Antibody production was shown to require the cooperative interaction of B and T cells. Poisson analysis of B cell precursor frequency showed that approximately 1 in 40,000 B cells could be induced to produce IgG anti-influenza virus antibody in virus-stimulated cultures. Further investigation of this in vitro response should allow dissection of the cellular mechanisms involved in the regulation of antibody production in man.

Antibodies, Viral↗
PubMed1981

In vitro production of anti-influenza virus antibody after intranasal inoculation with cold-adapted influenza virus.

We have studied the production of anti-influenza virus antibody in vitro by peripheral blood mononuclear cells (PBMC) obtained from 7 normal volunteers at various times after intranasal inoculation with cold-adapted A/Alaska/6/77 [H3N2] influenza virus. Antibody released into culture supernatants was assayed by a 2-step enzyme-linked immunosorbent assay (ELISA). Cells obtained 6 days after intranasal inoculation spontaneously released both IgG and IgA anti-influenza antibody; this antibody production occurred within 24 hr, was specific for the virus used to inoculate the volunteers, and was inhibitable by cycloheximide. When day 6 cells were cultured in vitro for 12 days with the polyclonal activator pokeweed mitogen (PWM), no increase in the amount of antibody above that released in the absence of PWM was seen. In contrast, cells obtained 27 days after inoculation made no spontaneous antibody. In addition, cultures of these day 27 cells with PWM resulted in the production of large amounts of IgG antibody but relatively little IgA anti-virus antibody. Thus, after a mucosal influenza virus infection, several subpopulations of functionally different cells sequentially appear in the peripheral circulation: an initial population of cells secreting IgG and IgA antibody spontaneously, followed by a 2nd population of cells secreting IgG antibody when stimulated with PWM.

Administration, Intranasal↗
PubMed1981

Resolution of longstanding protein-losing enteropathy in a patient with intestinal lymphangiectasia after treatment for malignant lymphoma.

In 1956 we evaluated a patient who had a debilitating disease of a 2 yr duration, characterized by recurrent vomiting, diarrhea, cachexia, massive edema, hypoproteinemia, and dilated intestinal lymphatics. During our initial evaluation of this patient, we observed that 42% of her circulating protein pool was lost into her gastrointestinal tract daily, whereas normal gastrointesinal loss of protein does not exceed 1.6%. Her disease appeared to represent a classic example of intestinal lymphangiectasia. She was treated symptomatically for 13 yr with essentially no change. In 1969 the patient developed a stage IV diffuse, undifferentiated (non-Burkitt's) malignant lymphoma. Using immunoperoxidase staining, the neoplastic cells were found to contain cytoplasmic IgMKappa, suggesting that the lymphoma had a monoclonal B-cell origin. She was successfully treated with cyclophosphamide, vincristine, and prednisone. Shortly after the initiation of this systemic combination chemotherapy, her serum protein concentration returned to normal, her edema resolved, and she was cured of gastrointestinal symptoms. Moreover, repeat studies revealed that her protein loss had fallen to only 2%. The simultaneous cure of both the intestinal lymphangiectasia and lymphoma with combination chemotherapy suggests new relationships between these conditions as well as new possibilities for the treatment of acquired forms of intestinal lymphangiectasis associated with overwhelming gastrointestinal protein loss.

Adult↗
PubMed1980

Small intestinal biopsies and HLA types in dermatitis herpetiformis patients with granular and linear IgA skin deposits.

In this study we determined whether dermatitis herpetiformis patients whose skin contained linear IgA deposits differ from those whose skin contained granular IgA deposits with regard to the presence of gluten-sensitive enteropathy and with regard to the prevalence of certain histocompatibility antigens. We performed multiple Rubin tube intestinal biopsies on 11 patients, 6 with linear and 5 with granular IgA deposits. The gut biopsies were evaluated histopathologically in a blinded fashion. We found that none of the patients with linear deposits (5 with lamina lucida and 1 with sub-basal lamina deposits) h-d detectable jejunal abnormalities whereas all of those with granular deposits had jejunal abnormalitites (villous atrophy and increased numbers of intraepithelial lymphocytes). In parallel studies HLA typing was performed in 10 patients with linear IgA deposits and in 49 patients with granular deposits. Only 30% of those with linear deposits had HLA-B8, a prevalence not significantly different from that of the normal population (24%); in contrast, 88% of those with granular deposits had HLA-B8, a prevalence significantly greater than in the normal population ( less than 0.001). We therefore conclude that patients with linear IgA deposits have a disease which is pathophysiologically different from those with granular IgA deposits.

Adolescent↗
PubMed1980

Gluten-sensitive enteropathy. Influence of histocompatibility type on gluten sensitivity in vitro.

We previously developed an in vitro organ culture system in which gluten exerts a toxic effect on intestinal mucosa of patients with active gluten-sensitive enteropathy. Gluten generally inhibits the epithelial cell maturation of intestinal biopsy specimens that otherwise occurs if the tissue is cultured for 24-48 h in a gluten-free medium. However, small intestinal mucosa from 15-20% of patients with proven gluten-sensitive enteropathy fails to manifest the expected gluten-induced damage in vitro. In the present study, we explored the relation between in vitro gluten-induced intestinal damage and the presence of HLA-B8. We determined whether the patients' histocompatibility type (HLA-B8 positive or negative) influenced the ability of gluten protein to inhibit epithelial cell maturation of cultured intestinal biopsy specimens from patients with gluten-sensitive enteropathy. Intestinal biopsies from 21 of 24 patients with gluten-sensitive enteropathy and HLA-B8 showed gluten-induced damage in vitro. On the other hand, intestinal biopsies from only 4 of 16 patients with gluten-sensitive enteropathy but without HLA-B8 showed gluten-induced damage in vitro. The difference in the effect of gluten in vitro between these two groups was statistically significant (P < 0.01). The data show a dichotomy between gluten-induced tissue damage in vivo and in vitro in HLA-B8 negative patients, suggesting that HLA-B8 is important for gluten to manifest a cytotoxic influence in organ culture.

Alkaline Phosphatase↗
PubMed1980

Deficiency of the autologous mixed lymphocyte reaction in patients with primary biliary cirrhosis.

In this study we show that patients with primary biliary cirrhosis (PCB) have a marked deficiency in the ability to generate an autologous mixed lymphocyte reaction (AMLR) but have a normal ability to generate an allogeneic mixed lymphocyte reaction (MLR). This deficiency is not due to differences in the time-course of the proliferative response or to an altered response to variable numbers of stimulator cells. The deficiency was consistently found irrespective of the methods used to isolate autologous stimulator cells. Both responder cells and stimulator cells obtained from patients with PBC were similar to normal cells in their ability to generate an MLR in allogeneic normal human serum. In addition, serum from patients with PBC inhibited the ability of normal lymphocytes to generate both the AMLR and MLR to a similar degree, suggesting that the defect of the AMLR in PBC is not due to a serum factor. It has been shown that the responder cell population in the AMLR contains a subpopulation of cells that mediate suppression. Therefore, it is possible that the deficiency of the AMLR may be related to previously described abnormalities of suppressor function in patients with PBC.

Adult↗
PubMed1980

Dermatitis herpetiformis: the skin and the gut.

Dermatitis herpetiformis is an intensely itchy, chronic, papulovesicular eruption that is usually symmetrically distributed on extensor surfaces. Histologically, it is characterized by dermal papillary collections of neutrophils and subepidermal vesicle formation. The skin has IgA deposits in areas corresponding to the earliest histopathologic change; that is, at the epidermal-dermal junction. Most patients have an associated asymptomatic gluten-sensitive enteropathy that mimics ordinary gluten-sensitive enteropathy (celiac disease) both morphologically and in its response to gluten protein. There is a marked increase in the prevalence of the major histocompatibility antigens, HLA-B8 and HLA-Dw3, and in certain B cell antigens in these patients. Although the sulfones or sulfapyridine have been the mainstay of treatment, it is now clear that the skin disease responds to strict adherence to a gluten-free diet. These findings are reviewed and from them are drawn certain conclusions as to possible pathophysiologic mechanisms involved in dermatitis herpetiformis.

Antigen-Antibody Complex↗
PubMed1979

T-cell regulation of murine IgA synthesis.

In studies reported here, the polyclonal activator lipopolysaccharide was used to stimulate the synthesis and secretion of IgM, IgA, and IgG in cultures of mouse lymphoid cells. The total immunoglobulin of each class which resulted was measured by specific double-antibody radioimmunoassays. The effect of Con A-activated T cells from various tissues on such immunoglobulin synthesis was then assessed. Variations in regulatory T-cell activity among the various lymphoid tissues for IgA but not for IgM or IgG was observed. In particular, Peyer's patches T cells were found to contain a high level of IgA T-cell helper activity compared to that of spleen or peripheral lymph node. The independent variation of T-cell regulatory activity for IgA as compared to that for IgM and IgG among the different tissues is most consistent with there being a separate subset of T cells specifically regulating IgA. The significance of these findings for the understanding of the secretory immune system is discussed.

Animals↗
PubMed1979

A receptor for IgA on human T lymphocytes.

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tmu receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.

Animals↗
PubMed1979

Fc receptors for IgA on human B, and human non-B, non-T lymphocytes.

Recently, receptors for IgA were demonstrated on subpopulations of human T lymphocytes. In this report, TNP-modified ox erythrocytes coated with the IgA myeloma MOPC-315 were used to detect IgA receptor-bearing lymphocytes within the human non T cell lymphocyte population. A mean of 5.3% (range 2.9 to 12.4%) of E-rosette negative human lymphocytes bound IgA-coated indicator cells. Blocking studies with soluble IgA, IgG, and IgM demonstrated that the IgA receptors on the non-T cell populations were separate and distinct from the Fc-receptors for IgG and IgM. Fractionation of the non-T lymphocytes on anti-human (Fab)2 columns into sIg+ and sIg- populations or by rosetting with EAC to provide CRL+ and CRL- populations demonstrated that Fc-IgA receptors were present on a subpopulation of sIg+, CRL+ lymphocytes, and also on sIg- (non-T, non-B) lymphocytes.

Animals↗