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Biomedical subjects

U Forsum

Publications and source records attributed to U Forsum.

At least 109 records · Page 6Linked to original sources

Immune functions of human synovial cells. Phenotypic and T cell regulatory properties of macrophage-like cells that express HLA-DR.

Normal and rheumatoid synovial cells have been analyzed in frozen sections and in suspension. HLA-DR-expressing, macrophage-like cells are demonstrated in normal synovial intima and in rheumatoid tissue. Suspended normal synoviocytes equaled peripheral blood non-T lymphocytes as stimulators of mixed lymphocyte reactions, whereas adherent rheumatoid synovial cells were extremely efficient as such stimulators and in presenting soluble antigens to autologous T lymphocytes. This HLA-DR-dependent T lymphocyte regulation might provide a cellular basis for the HLA-D haplotype-arthritis associations.

Antibodies, Monoclonal↗

Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis.

Originating from observations on similarities between the rheumatoid synovial tissue and skin lesions in delayed-type hypersensitivity reactions--similarities as to massive infiltrates of "helper" T lymphocytes close to HLA-DR-expressing macrophage/dendritic cells--a notion is formed on the importance of local macrophage-dependent helper T-cell activation in the rheumatoid joint similar to that in a delayed-type skin reaction. In vitro studies on suspended synovial cells have been used to test and qualify these ideas. It is shown that (i) HLA-DR-expressing cells in normal synovial intima can, like epidermal Langerhans cells, mediate T-cell activation; (ii) the large numbers of rheumatoid synovial HLA-DR-expressing macrophage-like/dendritic cells are heterogeneous and mediate either efficient activation or suppression of T-lymphocyte proliferation, and (iii) specificity of rheumatoid T cells can be analyzed with the help of autologous synovial antigen-presenting cells; a specific anti-collagen type II response is reported in three patients.

Arthritis, Rheumatoid↗

Enrichment of epidermal Langerhans cells: studies with a monolayer technique and flow cytometry sorting.

Langerhans cells were enriched from epidermal cell suspensions by a monolayer technique based on the association of Langerhans cells with solid matrix-bound anti-Ia antibodies or by flow cytometry sorting of fluorescein-isothiocyanate labeled anti-Ia reactive cells. The monolayer technique gave a moderate enrichment (15-37%) whereas considerably higher purity (73-87%) was obtained by flow cytometry sorting. The identity of the enriched anti-Ia reactive cells as Langerhans cells was established by histochemical techniques or electron microscopy. The monolayer-enriched Langerhans cells could function as stimulating cells in the mixed leukocyte culture reaction and as antigen-presenting cells.

Animals↗

Anti-Ia-reactive cells in the urinary tract of man, guinea-pig, rat and mouse.

Tissues from the urinary tract of man, the guinea-pig, mouse and rat were investigated for Ia (HLA-DR) tissue distribution with an immunohistochemical staining technique using anti-Ia monoclonal antibodies. Human and guinea-pig tissues were also investigated with a rabbit anti-human HLA-DR immunoglobulin. Ia-antigen-expressing cells were demonstrated in bladder connective tissue of man, the guinea-pig, rat and mouse. In man and the guinea-pig anti-Ia-reactive cells were present also in the bladder epithelium. In the kidney, the Ia antigens seemed to be restricted to the endothelium in man, the guinea-pig and mouse, whereas in the rat, the kidney contained anti-Ia-reactive dendritic cells in the interstitium. The staining of mouse tissues with anti-I-Ak- and anti-I-E/Ck-specific monoclonal antibodies revealed that cells of different Ia phenotypes were differently distributed in the bladder connective tissue. In sections from the mouse kidney no difference in staining was seen with the various antibodies. In experiments with mouse bone-marrow chimeras the anti-Ia-reactive cells in mouse bladder were shown to be of bone-marrow origin. In humans epithelial Ia-expressing cells could be isolated from the urine. Such cells might constitute a source of anti-Ia-reactive epithelial cells for future functional studies.

Animals↗

Demonstration of heat-labile antigen(s) of Bacteroides fragilis associated with non-homogeneous immunofluorescent staining.

Rabbit hyperimmune sera against nine Bacteroides fragilis strains were tested in indirect immunofluorescence against homologous and heterologous formalin and heat-treated bacterial cells. Strain-specific heat-stable and heat-labile antigens were demonstrated as well as many cross-reactive ones. Besides these findings a striking non-homogeneous fluorescence was noted, inasmuch as varying numbers of the bacterial cells were stained while others were not. Results of absorption experiments indicated that the reactive antigens were heat-labile. Non-homogeneous fluorescence was also demonstrated with sera from patients with clinically significant Bacteroides fragilis infections.

Animals↗

T lymphocyte subsets in the duodenal epithelium in dermatitis herpetiformis.

Monoclonal antibodies to human T lymphocyte subsets and HLA-DR antigens were used to characterize the intra-epithelial T lymphocytes and HLA-DR reactive cells in the duodenal epithelium in dermatitis herpetiformis (DH). The expression of HLA-DR antigens on the epithelial cells was similar in patients and controls. There were significantly more Leu 2a (suppressor/ cytotoxic phenotype) reactive cells, as related to epithelial length, in 7 patients with DH than in the epithelium of 5 controls. However, the ratio of Leu 2a (suppressor/cytotoxic phenotype) to Leu 3a (helper/inducer phenotype) reactive cells was the same in the patients as in the controls. Thus this study indicates that there is a quantitative rather than a qualitative difference in T lymphocyte subpopulations in duodenal epithelium between patients with DH and normal persons.

Adult↗

In situ identification of T lymphocyte subsets and HLA-DR expressing cells in the human skin tuberculin reaction.

T lymphocyte subsets and HLA-DR expressing cells were studied with an immunohistochemical double staining technique in frozen sections of human skin 6, 48 and 96 hr after intradermal PPD injections. The number of lymphocytes reacting with monoclonal Leu 1 antibodies (all mature peripheral T cells) increased with time. The majority of the T lymphocytes at 48 and 96 hr reacted with Leu 3a ('helper/inducer' phenotype) antibodies and a few with Leu 2a ('suppressor/cytotoxic' phenotype) antibodies. Apposition of T lymphocytes of both subsets to HLA-DR expressing cells occurred in the dermis as well as in the epidermis. The study gives a morphological picture of the cell-mediated immune reactions in delayed type of hypersensitivity consistent with in vitro experiments on proliferative responses to soluble antigens.

Adult↗

Appearance of anti-HLA-DR-reactive cells in normal and rheumatoid synovial tissue.

The reactivity of rabbit anti-HLA-DR antigen antibodies with cells in normal and rheumatoid synovial tissue was investigated by indirect immunofluorescence on frozen sections of tissue. The antibodies reacted with a significant proportion of the synovial lining cells of both normal and rheumatoid synovial tissue, with endothelial cells, and with a number of, most probably, migratory cells. After dispersion of cells from rheumatoid synovial tissue by digestion with collagenase and DNase, adherent cells of both a macrophage-like and a dendritic appearance reacted with the anti-HLA-DR antigen antibodies. The adherent cells were also found to be potent stimulators in the allogeneic MLR. In addition, it was found that a high percentage of T lymphocytes from both peripheral blood and synovial tissue of rheumatoid patients bound anti-HLA-DR antibodies. The present data suggest a role for synovial lining cells in HLA-D-locus-dependent events of importance in the pathogenesis of rheumatoid arthritis and other joint diseases and point to the need for further investigations on T lymphocytes derived from the site of inflammation in the study of rheumatoid arthritis.

Animals↗

Relationship between HLA-DR-expressing cells and T lymphocytes of different subsets in rheumatoid synovial tissue.

An immunohistochemical double staining technique was used to study the relationships between HLA-DR-expressing, mostly macrophage-like cells, and different populations of T lymphocytes in frozen sections of synovial tissue from patients with inflammatory joint disease, particularly rheumatoid arthritis. Substantial T-lymphocyte infiltration as measured by Leu 1 antibody binding was found, especially adjacent to HLA-DR-expressing cells near the synovial cavity and around small vessels. Most of the T cells reacted with Leu 3a ('helper/inducer'-cell-specific) antibodies, whereas relatively few cells were Leu 2a ('cytotoxic/suppressor' T-cell-specific)-positive.

Adult↗

T cell-mediated cytotoxicity induced by Listeria monocytogenes. II. Specificity of cytolytic effector cells.

Listeria monocytogenes- (LM) antigen-dependent cytotoxic lymphocytes, identified in a companion manuscript as T cells (CTL), can kill a wide variety of target cells, including syngeneic fibroblasts of both fetal and adult origin, and certain allogeneic and xenogeneic tumor cells. Cold target cell inhibition assays revealed that cells susceptible to lysis can block the cytolytic process in a dose-dependent manner, whereas lysis-resistant cells cannot. Several lines of evidence indicate that to realize their cytolytic potential, LM-dependent CTL must bind to their targets. Aggressor cells that adhere to susceptible target cell monolayers have enhanced cytolytic activity when compared with unfractionated cells or cells that do not adhere. LM-dependent CTL fail to kill when they are separated from susceptible targets by an agar barrier. Arguments against the complicity of a soluble mediator in the killing process derive from the rapid (within 3 hr) expression of cytotoxicity in circumstances where cell contact can occur, and the finding that spent medium in which LM-dependent CTL are either activated or assayed is devoid of cytolytic activity. The specificity of LM-dependent CTL suggests that these effector T cells recognize an as yet unidentified array of antigens that are expressed on a variety of rodent cells. Their cytolytic repertoire cannot be ascribed solely to the polyclonal activation of alloreactive T cells, because responder cells that have been negatively selected for a particular RT-1 haplotype can kill target cells bearing these alloantigens.

Animals↗

Hormonal regulation of the expression of Ia antigens on mammary gland epithelium.

Guinea pig and mouse mammary gland epithelial cells express Ia antigen-like molecules that react specifically with a rabbit anti-Ia antigen antiserum. The murine Ia antigen-like molecules were shown to share alloantigenic determinants with regular spleen cell Ia antigens. The expression of the mammary gland Ia antigens is under hormonal control, i.e. the Ia antigen expression is induced by pregnancy and lactation and can also be induced by the exogenous administration of lactotropic hormones.

Animals↗

Distribution of Ia-antigen-like molecules on non-lymphoid tissues.

Ia-antigen-like molecules are expressed on cells within several different non-lymphoid tissues of the guinea-pig. In indirect immunofluorescence analyses anti-Ia-antigen antibodies stained epithelial cells lining the intestinal tract, the bile ducts, the respiratory tract and the urinary tract. The rabbit antibodies against Ia antigens also stained the cells of the parotid and the submandibular glands. Evidence was also obtained suggesting that the reticuloepithelial cells of the thymus, like the Kupffer cells of the liver, express Ia-antigen-like molecules. In several cases indirect immunoprecipitation analyses and SDS-polyacrylamide gel electrophoresis confirmed the immunofluorescence studies inasmuch as Ia-antigen-like subunits with apparent molecular weights of 26,000 and 34,000 could be isolated from the non-lymphoid organs.

Animals↗