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Biomedical subjects

S R Webb

Publications and source records attributed to S R Webb.

At least 73 records · Page 4Linked to original sources

T cell lines with dual specificity for strong Mls and H-2 determinants.

To examine the relationship of T cell specificity for Mls vs H-2 determinants, BALB/c (H-2d,Mlsb)(d,b) T cells were stimulated repeatedly in vitro with H-2-compatible, Mls-incompatible DBA/2(d,a) stimulators. This line of T cells gave strong mixed-lymphocyte reactions to the priming Mlsa determinants but, in addition, gave appreciable responses to various foreign H-2 determinants. When this T cell line was subsequently stimulated over a period of 2 mo with Mlsa-negative cells of a particular foreign H-2 haplotype, e.g., H-2k, the cells gave high responses to H-2k determinants but only very low responses to third-party H-2 determinants. Significantly, the cells retained high reactivity for Mlsa determinants. In other experiments, BALB/c T cells positively selected to Mlsa,d-negative H-2-incompatible stimulator cells retained high reactivity for Mlsa determinants. The implications of these findings are discussed.

Animals↗

Morphological and histochemical analyses of two human T-cell subpopulations bearing receptors for IgM or IgG.

Two subpopulation of circulating human T cells forming rosettes with neuraminidase-treated sheep erythrocytes were purified on the basis of the presence of receptors for IgG (TG cells) or for IgM (TM cells), and were shown to have distinguishing morphological and histochemical characteristics. TM cells had the general features of typical small- or medium-sized lymphocytes; most were easily identifiable by distinctive cytoplasmic accumulations, usually one and sometimes two large spots, of nonspecific acid esterase activity. The release of the vesicular contents on short-term culture of TG cells was inhibited by cytochalasin B. Definition of these distinguishing characteristics of TM and TG cells provides a basis for practical enumeration of these functionally distinct subpopulations of human T cells. Some of the TG cells were capable of endocytosis of IgG antibody-coated erythrocytes.

Binding Sites, Antibody↗

Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG.

Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.

Antibody-Producing Cells↗

Imbalances in T cell subpopulations associated with immunodeficiency and autoimmune syndromes.

Abnormal proportions of the distinct T cell subpopulations binding the Fc portion of IgM (T-M) cells and those bearing receptors for the Fc portion of IgG (T-G) cells, were observed in blood samples from patients who had congenital or acquired abnormalities of the thymus, severe combined immunodeficiency, or an unexplained primary deficiency in cell-mediated immunity; most had too few circulating T-M cells and often an overabundance of T-G cells. In an in vitro evaluation of lymphocyte from one of three thymoma patients with an elevated T-G subpopulation, removal of T-G cells abrogated the suppression of T-M cell help of B cell differentiation induced by pokeweed mitogen. A spectrum of patients with sex-linked infantile agammaglobulinemia, variable hypogammaglobulinemia, and selective IgA deficiency, and a few patients with autoimmune syndromes infrequently had distorted representation of these T cell subpopulations in the circulation. This suggests that B cell dysfunction in many of these patients is not merely due to numerical excesses or insufficiencies of helper or suppressor T cells.

Autoimmune Diseases↗

Susceptibility of mice to group B coxsackie virus is influenced by the diabetic gene.

A positive correlation was found between genetic predisposition to diabetes in the mouse and susceptibility to group B Coxsackie virus in this host. Male mice of the inbred strain C57BL/Ks and the following genetic variants were used; mice homozygous for the autosomal recessive gene for diabetes (db/db), the phenotypically normal heterozygous (db/+), and the normal mice which lacked the diabetic gene (+/+). The mortality response of the +/+ mice to intraperitoneal inoculation with Coxsackie virus B4 differed from the response of the two genetic variants (db/db and db/+) derived from this strain. The db/+ variant was more susceptible to Coxsackie virus B4 than the parental background strain (+/+). The db/db variant was more susceptible than either of the other genotypes. Pathological findings of the pancreas of the three genotypes during the acute stage of infection closely paralleled the genotypically dependent susceptibility of the host.

Animals↗

Inhibition of dihydrofolate synthetase by folate, homofolate, pteroate and homopteroate and their reduced forms.

Dihydrofolate (H2-folate) synthetase (EC 6.3.2.12) was isolated from Escherichia coli B. A radiochemical assay was developed to determine the activity of H2-folate synthetase in order to study the effects of folate metabolites and antimetabolites which would interfere with the microbiological assay method previously used. The effects of folate and pteroate derivatives on the activity of this enzyme were investigated to determine if inhibition of this enzyme could constitute a site of action for these compounds as chemotherapeutic agents or a site of metabolic regulation. H2-folate synthetase was inhibited by its product, H2-folate, and by the antimetabolite dihydrohomopteroate, with apparent Ki values of 23.4 and 9.2 muM, respectively.

Escherichia coli↗

Subpopulations of human T cells identified by receptors for immunoglobulins and mitogen responsiveness.

Human T lymphocytes in peripheral blood have been shown to have receptors for IgG (Tgamma) or IgM (Tmu). Cultured Tgamma cells do not express receptors for IgM and purified Tmu cells do not have receptors for IgG, thus they appear to be distinct T cell populations. Although the two subpopulations show similar response patterns to concanavalin A, Tmu and Tgamma cells exhibit different dose-response curves to phytohemagglutinin. The normal response pattern to phytohemagglutinin requires a mixture of T cell subpopulations suggesting that synergistic interactions may occur.

Binding Sites, Antibody↗

T- and B-cell interactions in autoimmune syndromes.

We have reviewed briefly some of the individual capabilities of T and B cells and how these can be modified by interactions between the two cell lines. Evidence that T cells have their own distinct receptors for antigens, yet under certain circumstances may bind IgM or IgG produced by B cells, has been particularly emphasized. The probability that B cells, in turn, may bind the antigen receptor of T-cell origin reflects the balanced nature of an intricate communication system in which interactions between antigens, antigen receptors, and binding sites for these receptors all serve to modulate the integrated functioning of T and B cells. It is suggested that this communication system is disturbed in patients with rheumatoid arthritis; specifically, it is proposed that defective feedback activity of IgG-antigen complexes on activated T cells may exist in some patients and could result in unchecked and harmful T-cell activity in the joint. Therapeutic implications of this idea are mentioned.

Animals↗

Isolation of chikungunya virus contaminating an Aedes albopictus cell line.

An Aedes albopictus cell line was found contaminated with structures morphologically compatible with an alphavirus. Rapid isolation of a cytopathic virus was effected by combining sonication, concentration with Aquacide II-r, rate zonal sedimentation and subsequent plating of fractions on Vero cells under agar overlay. The virus caused neithedeath nor disease on inoculation into infant and adult mice. It produced a c.p.e. in Vero and BHK 21 cells, and multiplied in Singh's Aedes aegypti cells. The virus was identified serologically as chikungunya by complement-fixation and plaque reduction netralization test. Virus was not detected in a single attempt by these methods in the American Type Culture Collection A. albopicturs line. The presence of chikungunya virus in A. albopictus cells is not easily recognized and may complicate interpretation of experimental results.

Aedes↗