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Biomedical subjects

J D Stobo

Publications and source records attributed to J D Stobo.

At least 55 records · Page 3Linked to original sources
PubMed1981

Antigen-reactive T cells can be activated buy autologous macrophages in the absence of added antigen.

T cells responsive to macrophages (M phi) in the autologous mixed lymphocyte reaction (AMLR) contain those cells that can be induced to proliferate by soluble antigens. Negative solution (5-bromo-2-deoxyuridine and light) of T cells activated by autologous M phi also removed those cells required for reactivity to Candida albicans and purified protein derivative. Positive selection of T cells responsive to autologous M phi yields a population that is simultaneously enriched in antigen reactivity. Some patients demonstrating cutaneous anergy and diminished in vitro blast transformation in response to soluble antigen also lack T cells responsive to the AMLR to M phi. When considered in conjunction with previously reported data, these findings indicate the AMLR occurring between T cells and M phi in the absence of soluble antigen represents self recognition occurring between antigen-reactive T cells and antigen-presenting M phi.

Animals↗
PubMed1981

Regulation of immune reactivity to collagen in human beings.

Denaturated beef collagen was tested for its ability to induce the production of leukocyte inhibition factor among the peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal individuals. Responsiveness, defined as the production of leukocyte inhibition factor sufficient to cause greater than 20% inhibition of leukocyte migration, was significantly (P less than 0.001, X2 = 31.1) associated with HLA-DR4. All HLA-DR4 positive individuals, including subjects without any evidence of synovitis, were collagen responders. There was no significant (P = 0.3) difference in the absolute reactivity of HLA-DR4+ versus HLA-DR4- individuals to respond to another antigen, Candida albicans. Collagen reactivity required interactions between macrophages and T cells and was directed against determinants inherent in the linear polypeptide, (Gly-Pro)n. In 5 normal HLA-DR4- nonresponders tested, absence of discernable reactivity to collagen was associated with the presence of antigen-specific, radiosensitive suppressive T cells. These studies suggest that during the physiologic metabolism of collagen all individuals are exposed to Gly-Pro determinants normally buried in the interstices of the collagen triple helix. In individuals whose major histocompatibility complex contains genes linked to those coding for HLA-DR4, this results in the activation of reactive T cells. Conversely, in individuals lacking these genes, collagen-specific suppressive cells predominate.

Animals↗
PubMed1981

Cellular, molecular, and genetic characteristics of T cell reactivity to collagen in man.

Rheumatoid arthritis is significantly associated with the HLA determinant HLA-DRw4 and cell-mediated reactivity to collagen. To determine if genes linked to those coding for HLA-DRw4 constituted immune response genes for collagen reactivity, peripheral blood mononuclear cells from 20 individuals with rheumatoid arthritis, 13 individuals with other arthropathies, and 41 normal individuals were compared for their ability to synthesize the lymphokine leukocyte inhibition factor in response to denatured bovine collagen. All individuals were responsive to the control antigen Candida albicans. While 90% of the patients with rheumatoid arthritis responded to collagen, so did 30% of the individuals without rheumatoid arthritis. This included 15 normal individuals without any evidence of arthritis. Collagen responsiveness was dependent on interactions between T cells and macrophages was dependent on interactions between T cells and macrophages and was directed against determinants expressed by primary amino acid sequences in the synthetic polypeptide (Gly-Pro)n. HLA-DRw typing of 59 individuals revealed a highly significant relationship (P less than 0.0001, chi 2 = 33.7) between HLA-DRw4 and collagen responsiveness, irrespective of whether or not rheumatoid arthritis was present. All normal individuals who were HLA-DRw4-positive were collagen responders. These studies demonstrate that the cellular, molecular, and genetic characteristics of collagen reactivity in man parallel those documented for the T cell-dependent response to antigens under immune response gene control in rodents.

Arthritis, Rheumatoid↗
PubMed1980

Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells.

Utilizing somatic cell hybridization, we have developed a monoclonal antibody that interacts only with cells of the monocyte/macrophage (M phi) line and not with other myeloid or lymphoid cells. This antibody detects a 120,000-dalton determinant present on 37 +/- 2.8% of the peripheral blood M phi from several (HLA-DR)-disparate individuals and only depicts a subpopulation (approximately 30%) of HLA-DR-bearing M phi from any single subject. Cytolytic removal of this subpopulation of HLA-DR-bearing cells markedly diminished antigen-induced T cell reactivity, a deficiency that can be reconstituted with autologous M phi but not with either their soluble products containing lymphocyte-activating factor or with intact HLA-DR-disparate M phi. Whereas M phi bearing both the 120,000-dalton determinant and HLA-DR serve as effective stimulators for autologous mixed lymphocyte reactions. M phi bearing only HLA-DR determinants do not. However, this latter population of M phi can stimulate proliferation among alloreactive T cells. These studies indicate that the Mac-120 monoclonal antibody detects a subpopulation of HLA-DR-bearing M phi that is required for the genetically restricted presentation of conventional antigen to reactive T cells. Within the M phi population, these Mac-120+ cells constitute the most effective stimulators for autologous mixed lymphocyte reactions.

Antigens, Surface↗
PubMed1980

In vitro synthesis of prostaglandins and related lipids by populations of human peripheral blood mononuclear cells.

This report focuses on the identification of the human peripheral blood mononuclear cells that do or do not produce prostaglandins (PGs) and related arachidonic acid metabolites. Our results, using two different assay systems, indicate that the monocyte/macrophage (Mphi) is the major and possibly sole source of thromboxane (TXB2) and prostaglandin E2 (PGE2) among peripheral blood mononuclear cells. Adherent peripheral blood monocytes (> 95% esterase positive) produced substantial amounts of these compounds. Quantitation of products which had incorporated exogenous 14C-arachidonic acid and radioimmunoassay of adherent cell culture fluids demonstrated that the amount of TXB2 produced by these cells was appreciably greater than the amount of PGE2 produced. Additional confirmation of TXB2 synthesis was shown by abolishing the TXB2 peak on TLC and TXB2 activity detected by RIA by treating cells with a specific inhibitor of thromboxane synthetase. In contrast, non-adherent T cells failed to synthesize either PGE2 or TXB2. Non-adherent B cells (95% Ig positive) incubated with 14C-arachidonic acid produced a small peak of radioactivity co-chromatographing with TXB2, and no PGE. All three cell populations incorporated similar amounts of 14C-arachidonic acid into hydroxy-fatty acids. We were unable to detect 6-keto-F1 alpha, the hydrolysis product of prostacyclin (PGI2) in any of the cell types tested. The absence of PG synthesis among normal peripheral blood T and B cells was also noted among established human lymphoid cell lines. Neither a human T (CCRF), nor a human B-cell line (GM-130), produced PGE2 or TXB2. Three murine macrophage cell lines, P388D1, J774.2, and WEHI-3 produced PGE2 and the latter TXB2 as well.

Animals↗
PubMed1980

Prostaglandin E2 as a modulator of macrophage-T lymphocyte interactions.

Sufficient data exist to implicate the monocyte-macrophage as the major source of prostaglandins in monocyte-macrophage-T lymphocyte interactions. Prostaglandin (PG) E2, a major prostaglandin synthesized by human monocyte-macrophages is able to modulate a variety of T lymphocyte reactivities including blastogenesis, lymphokine secretion, and cytotoxicity. The effect of PGE2 on T lymphocyte function varies according to the primary activating stimulus, the specific response under investigation, as well as the population of T lymphocytes involved. Some immunologic abnormalities found in clinical disease may in part derive from alterations occurring in the synthesis of PGE2 by monocyte-macrophages or in the response of T lymphocytes to PGE2.

Humans↗
PubMed1980

Genetic control of the murine T lymphocyte proliferative response to collagen: analysis of the molecular and cellular contributions to immunogenicity.

The genetic control of the murine immune response to denatured beef type II collagen was examined in an antigen-presenting cell-dependent T cell proliferation assay. It was found that the response to collagen is under the control of H-2-linked Ir genes, possibly operating at the level of the antigen-presenting macrophage. Utilizing in vitro cross-stimulation with synthetic collagen-like polypeptides, the data suggest that the antigenic determinants stimulating collagen immune T cells are more dependent on primary amino acid sequence and less on conformation. The implications of such findings for Ir gene specificity and other related immunologic functions is discussed.

Animals↗
PubMed1979

Specificity and function of a human autologous reactive T cell.

Normal human peripheral blood contains a population of T cells (autologous reactive cells [ARC]) capable of proliferating in response to signals from autologous B cells and monocytes. Selective suicide of proliferating ARC with 5-bromo-2-deoxyuridine and light demonstrated that this ARC was responsive to signals coded for by genes more closely linked to the HLA-DR, than to the HLA-A, or HLA-B, loci. Density-gradient fractionation of T cells indicated that populations enriched in ARC reactivity were also enriched for helper influences required for Ig synthesis by autologous B cells. In contrast, populations negatively selected for proliferating ARC were deficient in helper activity. These studies indicate that the ARC is responsive, at least in part, to products of genes closely linked to the HLA-DR locus and can function as a helper cell.

B-Lymphocytes↗