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N Tidman

Publications and source records attributed to N Tidman.

30 records · Page 2Linked to original sources

The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts.

Treatment with cyclosporin A (CyA) produces a reversal of the normal ratio of OKT4+ (inducer type) to OKT84 (suppressor-cytotoxic type) cells so that renal allograft recipients on CyA alone develop a four-fold increase in the absolute number of circulating OKT8 positive cells. Conventional immunosuppression with azathioprine and prednisolone reduces both populations of T cells without altering the ratio of OKT4+ to OKT8+ cells. This effect of CyA may help to explain its action as an immunosuppressive agent.

Azathioprine↗

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗

Enzymes of purine metabolism in human peripheral lymphocyte subpopulations.

Ecto-5'nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and deoxycytidine (CdR), deoxyguanosine (GdR), deoxyadenosine (AdR) and adenosine (AR) kinases have been measured in subpopulations of peripheral blood lymphocytes of eight healthy volunteers. The separation of B, T, T helper/inducer and T suppressor/cytotoxic cells was performed by means of density gradient centrifugation, E rosetting, passage through a nylon-wool column and antibody affinity chromatography utilising OKT8 and OKT4 monoclonal antibodies. ADA was significantly higher in T lymphocytes and 5'NT in B lymphocytes. Among T cell subpopulations, 5'NT activity was significantly higher (P less than 0 . 01) in T suppressor/cytotoxic (OKT8+) cells (32 . 9 units/10(6) cells than in T helper/inducer (OKT4+) cells (9 . 7 units/10(6) cells). Indeed, the 5'NT activity in T suppressor cells was similar to that in B cells. T helper cells tended, however, to have higher PNP and ADA activities than T suppressor cells but the differences were not statistically significant. No major differences were noted in kinase activities between any of the lymphocyte subpopulations.

5'-Nucleotidase↗

Distinct T lymphocyte subsets affect granulo-monocytic differentiation and proliferation.

Bone marrow culture techniques using semi-solid support-media provide an opportunity to observe granulocyte-macrophage progenitor cells proliferating and differentiating in vitro. Cells from the bone marrow and peripheral blood produce specific growth factors which stimulate both the proliferation and differentiation processes (collectively termed colony-stimulating factors or activity, CSF/CSA). Even highly purified CSA induces proliferation and concomitant differentiation suggesting that the two processes are inseparable. We here present evidence to suggest that the two processes are, at least in part, individually regulated. We observed delayed differentiation by morphological, cytochemical and functional criteria in granulocyte-macrophage clones formed in cultures in which the growth stimulus was supplied by marrow or blood cells which have been depleted of T lymphocytes bearing the OKT3/MBG6 antigen(s) by complement lysis. The proliferation stimulus was unaffected. T cell depletion using another monoclonal antibody, OKT11a (which removed an overlapping but not identical population of T cells), did not produce the same effect but did increase the level of CSA produced by the remaining marrow cells. Selective replacement experiments using OKT4+ or OKT8+ cell preparations suggested that removal of an MBG6+, OKT3+, OKT8+, OKT4-lymphocyte subset is responsible for the effect on differentiation.

Antibodies, Monoclonal↗

Increased numbers of cells with suppressor T cell phenotype in the peripheral blood of patients with infectious mononucleosis.

Peripheral blood cells from six patients with acute infectious mononucleosis were studied by two-colour immunofluorescence using antibodies to human T cells, inducer and suppressor-cytotoxic T cell subsets and Ia-like antigens. The absolute number of T cells with the suppressor-cytotoxic phenotype was substantially increased in each case; many of these cells also expressed Ia-like antigens and had the morphology of the large atypical cells characteristic of infectious mononucleosis. These activated suppressor T cells of infectious mononucleosis may therefore represent a control mechanism to prevent viral-induced proliferation of B cells.

Cytotoxicity Tests, Immunologic↗

Delineation of human thymocyte differentiation pathways utilizing double-staining techniques with monoclonal antibodies.

Three new techniques have been introduced for the phenotypic analysis of human thymocytes and T cells. Monoclonal antibodies of different subclasses (i.e. IgG1 and IgG2) were used in various combinations and labelled with subclass-specific second layers conjugated to different fluorochromes. Tissue sections were studied with combinations of monoclonal and conventional reagents, and anti-mouse Ig-coated macrobead columns were used to separate antibody-tagged cells. With the help of these simple techniques, four stage of thymocyte differentiation (prothymocyte, cortical, intermediate and medullary cell types) can be described in detail and the microanatomical relation of T cell subsets with other cell types studied.

Antibodies, Monoclonal↗

Recognition of a human T-lymphocyte differentiation antigen by an IgM monoclonal antibody.

A monoclonal antibody directed at a determinant on human T cells was produced and characterized. This IgM antibody, MBG6, bound to human peripheral blood T lymphocytes and to medullary thymocytes. It was unreactive with normal B cells, B-cell lines and granulocytes. Apart from T lymphocytes, bone marrow cells (including cells positive for the terminal transferase marker, myeloid colony-forming cells, myeloblasts, and differentiating myeloid and erythroid cells) were negative. Peripheral blood cells that were treated with MBG6 and rabbit complement were no longer capable of proliferating in response to phytohaemagglutinin or concanavalin A; MBG6 did not have any direct mitogenic action on T lymphocytes. Double immunofluorescence studies using IgM MBG6 and OKT3, and IgG2a monoclonal antibody that recognizes all peripheral T cells, showed that these two antibodies identified exactly the same cell populations. Competitive binding studies, however, indicated that MBG6 and OKT3 recognized different epitopes. The antibody may have clinical applications in bone marrow transplantation.

Animals↗

Distribution of t lymphocyte subsets in the human bone marrow and thymus: an analysis with monoclonal antibodies.

A panel of reagents (OKT1, 3, 4, 6, 8, and 11) detects differentiation antigens expressed exclusively on HuTLA+ T lymphoid cells but absent on bone marrow precursors, such as terminal deoxynucleotidyl transferase- (TdT) positive cells, immature myeloblasts, and other myeloid/erythroid cell types. In the bone marrow no transitional forms could be detected between TdT+ and T cells. The BM T cells showed mostly the suppressor/cytotoxic phenotype (OKT8+) with only a few T cells of inducer type (OKT4+). Thymocyte heterogeneity was also analyzed directly in tissue sections and in double labeling assays in combination with TdT staining, a marker for cortical thymocytes. Many large thymic blasts (in fetal and infant thymus) showed reactivity with OKT11--a pan-T reagent, but had only weak or negligible activity with the other antibodies. Cortical thymocytes reacted strongly with OKT11, 6, 4, and 8, whereas medullary cells reacted with OKT11, 3, 4 (majority) and 8 (minority). Thus, the reactivity with these antibodies is generated in the thymus at various stages of differentiation. In contrast, OKT10 (an anti-"precursor cell" reagent) reacted not only with thymocytes but also with TdT+ BM precursors, myeloblasts, and BM B lymphocytes although it was unreactive with mature peripheral lymphoid and maturing myelo/erythroid cells.

Adolescent↗