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Biomedical subjects

M A Bach

Publications and source records attributed to M A Bach.

At least 109 records · Page 6Linked to original sources

Monoclonal antibody-defined immunoregulatory cells in multiple sclerosis cerebrospinal fluid.

To determine if previously reported peripheral blood suppressor cell defects are also found in the central nervous system (CNS) of patients with multiple sclerosis (MS), we studied cerebrospinal fluid (CSF) and peripheral blood lymphocytes from 40 MS patients and 15 patients with other neurological diseases. With an indirect immunofluorescence technique using the OKT series of monoclonal antibodies (OKT4, marking helper/inducer cells, OKT5 and OKT8 marking suppressor/cytotoxic cells, and OKT3 marking all peripheral T cells) we found that MS patients tested in the first 2 wk of exacerbation had invariably diminished CSF suppressor/cytotoxic cells, which was followed by an elevation of these cells in the 3rd wk of exacerbation. Repeat studies of three patients showed that perturbations of CSF suppressor/cytotoxic cells were dependent on clinical status. These observations add to the accumulating data that suggest altered immunity in the pathogenesis of MS.

Antibodies, Monoclonal↗

[T-lymphocyte subpopulations in chronic inflammatory rheumatism].

Monoclonal antibodies to a series of human lymphocytes subpopulations antigens (OKT) specific of the peripheral T cells (OKT3), of the inducer population (OKT4) of the suppressor cytotoxic population (OKT 5, OKT8), and anti-Ia (OKI1) were used to study blood lymphocytes from 50 patients with active or inactive rheumatoid arthritis (RA) and from 23 patients with ankylosing spondylitis (AS). In RA patients, there is a significant decrease of the total T cell population (T3 +) with higher percentages of helper (T4 +) T cells than in controls. In active forms of the disease, there also is a decrease in the suppressor cytotoxic (T5 + and T8 +) subset with a significant increase of the immunoregulating ratios T4 +/T5 + or T4 +/T8 +. Elevated levels of Ia + lymphocytes are found in all RA patients. Corticosteroid treatment seems to erase these abnormalities. On the contrary in AS patients, no significant modification of the T cell populations was evidenced.

Antibodies, Monoclonal↗

Imbalances in T cell subpopulations in lepromatous leprosy.

Circulating T cells, T helper, and T suppressor cells were investigated in 24 lepromatous patients, using murine hybridoma-derived monoclonal antibodies OKT 3, OKT 4, and OKT 8. Six bacillary lepromatous patients without recent eNL were studied; in this group, suppressor cells were increased and helper cells diminished, resulting in a decrease in the helper/suppressor (H/S) ratio. Nine bacteriologically negative lepromatous patients without recent ENL were studied. T cell subsets distribution was normal, although some T cell functions were affected. It was further shown that in non-ENL patients, the diminution of the H/S ratio is correlated with the Bacteriologic Index (BI). Although bacillary, ENL patients exhibit a completely different T cell pattern than non-reactional patients. In these patients, there was a significant diminution of circulating suppressor cells, and an increase in T cell functions. These abnormalities were transient. Our results confirm the importance of suppressor cells in lepromatous leprosy, and suggest that imbalance between helper and suppressor cells may play a role in the pathogenesis of ENL reactions.

Adolescent↗

Immune response to phosphorylcholine. IX. Characterization of hybridoma anti-TEPC15 antibodies.

Hybridoma antibodies against the PC-binding T15 BALB/c myeloma protein were raised by cell fusion with anti-T15 A/He immune cells. The idiotype specificity of these monoclonal anti-T15 antibodies was determined with a panel of different myeloma and hybridoma immunoglobulins. Two types of anti-T15 antibodies are seen. One reacts with a number of different IgA myeloma proteins and with serum IgA of certain strains of mice; this reactivity most likely is due to allotypy. The other group consists of anti-T15 antibodies that are specific for the T15 idiotype and are therefore termed anti-idiotypic. The bindings of the anti-idiotype antibodies to T15 were specifically inhibited by T15 (F(ab')2 but not by other PC-binding myeloma proteins of different idiotypes. The relationship of the idiotype-specific anti-T15 antibodies to the PC-binding site of the T15 idiotype was analyzed by hapten inhibition of anti-idiotypic binding and by inhibition of BALB/c anti-PC splenic hemolytic plaque formation. Anti-T15 antibodies, for which the T15 binding is inhibited by PC or PC-BSA, also specifically inhibit anti-PC plaque formation. These antibodies are labeled site and near-site anti-idiotypic antibodies. Site and near-site-specific anti-idiotypic antibodies recognize different idiotopes on the T15 molecules. The possible differential biologic activities of these anti-idiotopes in idiotype network regulation is considered.

Animals↗

Imbalance in T cell subsets in human diseases.

T cell subsets have been evaluated in 232 patients with various immunological diseases and 41 normal individuals used as a control group. An increase in the helper/suppressor ratio (OKT4:OKT8) was often noted in multiple sclerosis (acute attacks and progressive forms), autoimmune hemolytic anemia (without steroids), membranous and IgA-deposit glomerulonephritis, HBs-negative chronic active hepatitis, lepromatous patients with erythema nodosum, and myasthenia gravis. Ratios were usually normal in membranoproliferative nephritis, in lupus erythematosus (at least in steroid treated cases) and in nephrotic syndrome. High values of helper cells have been found in Sezary's syndrome (with low or no suppressor cells) and in mycosis fungoides. Variable data have been obtained in immunodeficiency syndromes. These data have been correlated with age, sex and clinical parameters, as well as with other immunological tests (E rosettes, mitogen responses, mixed lymphocyte reaction, Concanavalin A-induced suppression). From our investigations we have concluded that the study of OKT antibody-defined T cell subsets offers a valuable technique for the further investigation of human immunological diseases.

Anemia, Hemolytic, Autoimmune↗

Abnormalities of T-cell subsets in glomerulonephritis and systemic lupus erythematosus.

In this study, three kinds of monoclonal antibodies directed at human T lymphocytes, produced by mouse hybridomas and termed OKT3, OKT4, and OKT8, were used in an indirect immunofluorescence assay, to analyze the distribution of peripheral T lymphocyte subsets in 41 patients with glomerulonephritis (GN) and 11 patients with systemic lupus erythematosus (SLE). As assessed by functional studies, OKT4 and OKT8 defined the helper and cytotoxic/suppressor T lymphocytes subsets, respectively, whereas OKT3 recognized all peripheral T-cells. Among GN patients, the ones presenting membranous GN (MGN), IgA disease, and lipoid nephrosis associated with segmental and focal hyalinosis (FGS) showed significant decrease of their peripheral cytotoxic/suppressive T cells. On the contrary, no significant alteration was found in the peripheral T cell distribution of patients with membranoproliferative GN (MPGN) and lipoid nephrosis associated with minimal-change GN (MCGN). Unexpectedly, there was a tendency for peripheral cytotoxic/suppressive T lymphocytes to be high in the majority of SLE patients, and only two of these subjects exhibited a relative decrease in peripheral OKT8 marked cells. The steroid therapy received by our patients might account for this discrepancy with previous reports of altered suppressor function in active SLE.

Adolescent↗

T-cell subset analysis by monoclonal antibodies in primary immunodeficiencies.

T-cell subsets have been analysed in 23 cases of primary immunodeficiency with monoclonal antibodies. Functional assays investigating T-cell function--proliferative response to mitogens, antigens, and allogeneic cells, cytotoxicity generated against allogeneic target cells and helper function to pokeweek mitogen-induced immunoglobulin synthesis--were performed in parallel in the same patients. The results enabled us to delineate four groups of patients. The first group consisted of patients in whom marker and function studies show concordant data, with either normal or strongly decreased T-cell number and function. The second group consisted of patients in whom various degrees of functional abnormality coexist with subnormal T-cell number and increased suppressor T-cell proportion. In the third group, we collected all patients who showed functional deficiencies without marker abnormalities. Finally, there was a small group composed of patients whose T-cell pattern was strongly suggestive of abnormal differentiation.

Adenosine Deaminase↗

Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies.

Functional T cell subsets have been evaluated in the peripheral blood of patients with myasthenia gravis using monoclonal anti-T cell antibodies and a suppressor cell assay based on the suppression of the mixed-lymphocyte reaction by concanavalin A-activated lymphocytes. A significant decline of suppressor cells was found in a large proportion of patients, both by direct count using the anti-suppressor-cytotoxic T cell antibody (OKT8) and by the suppressor assay. Patients also showed an increase in immature T cells defined by their simultaneous reaction with the anti-helper cell (OKT4) and anti-suppressor cell (OKT8) antibody. Thymectomy tended to enhance the deficit in suppressor cells, and to induce the disappearance of double-labelled cells.

Adolescent↗

Studies on T cell subsets and functions in leprosy.

T cell subsets and T cell functions were explored in 31 leprosy patients with the following methods: determination of the percentages of the different T cell subpopulations defined by monoclonal antibodies directed at total T cells, helper T cells and suppressor/cytotoxic T cells; measurement of the in vitro proliferative responses to mitogens; study of the concanavalin A-induced suppressive activity, assessed on MLC; measurement of delayed-type hypersensitivity by skin testing. The confrontation between immunological lepromatous patients without type-2 reaction (erythema nodosum leprosum), (2) lepromatous patients without ENL (erythema nodosum leprosum), (2) lepromatous patients was recent ENL and (3) tuberculoid patients. Unexpectedly, groups 1 and 3, although differing strongly in their clinical status and their sensitivity to lepromin (absent in group 1 and strong in group 3), showed a similar immunological profile with a normal percentage of T cells and a normal distribution of T cells among the major T cell subset contrasting with a moderate decrease of proliferative responses to mitogens and impaired delayed-type hypersensitivity reactions. Concanavalin A-induced suppressive activity was type-2 reaction) strongly differed from both other groups, showing striking abnormalities other groups, showing striking abnormalities of the repartition of the T cell subsets, with increased percentages of helper T cells and decreased percentages of suppressor T cells, and elevated proliferative responses to mitogens. Concanavalin A-induced suppressive activity was reduced in most patients of this group. It is suggested that this imbalance between T cell subsets contributes to the occurrence of ENL reactions in lepromatous patients.

Adolescent↗

The use of monoclonal anti-T cell antibodies to study T cell imbalances in human diseases.

Monoclonal antibodies are now available to evaluate human T cell subsets by direct counting using indirect immunofluorescence analysis. The critical use of these antibodies has already permitted the delineation of the T cell imbalances present in a number of immunologically mediated diseases such as autoimmune haemolytic anaemia, chronic active hepatitis, myasthenia gravis, glomerulonephritides, multiple sclerosis, leprosy, or immunodeficiency syndromes. The potential diagnostic and therapeutic application of this new methodology are emphasized.

Aging↗

Deficit of suppressor T cells in active multiple sclerosis.

Suppressor T cells in forty-seven patients with multiple sclerosis (MS) were studied by indirect immunofluorescence by means of monoclonal antibodies directed at T-cell subsets. Suppressor cell numbers were depressed in patients with acute exacerbation of MS and in patients with continuous progressive deterioration. In one case the T-cell anomaly was observed one week before the onset of the acute phase; it had been absent 4 months before exacerbation.

Acute Disease↗

Effect of long-term treatment with circulating thymic factor on murine lupus.

Mice from three different strains (NZB, B/W, and Swan) which spontaneously develop a lupus-like disease and show a premature decline of their secretion of the circulating thymic factor, Facteur Thymique Sérique (FTS), were treated repeatedly with FTS and followed for the evolution of their autoimmune disease. The autoimmune sialoadenoitis (Sjögren's syndrome) appearing in NZB and B/W mice, evaluated here by a scintigraphic method, was completely prevented or even cured by FTS treatment. The increase in anti-erythrocyte autoantibody production was transiently delayed in aged NZB mice. Conversely, antiDNA antibody production either remained unaffected or was accelerated (in B/W mice) by FTS treatment. These results demonstrate that the restoration of the failing thymic secretion does influence autoantibody production, in a manner depending primarily on the autoantigen eliciting the autoimmune response. However, caution is urged in the application of this approach to human lupus without further studies.

Age Factors↗

Thymic function in NZB mice. III. Impairment of the activity of specific suppressor cells involved in the regulation of antibody production against sheep red blood cells.

Spleen cells from DBA/2 mice immunized with high numbers of sheep red blood cells specifically suppress the primary anti-SRBC antibody response of syngeneic recipients specifically suppress the primary anti-SRBC antibody response of syngeneic recipients after in vivo transfer. Such suppressive activity of the immune spleen cells is mediated by null cells, or by T cells resistant to the cytotoxic activity of anti-Thy 1.2 antiserum plus complement. The primary anti-SRBC antibody response is much higher in NZB mice than in DBA/2 mice, and the suppressive activity of syngeneic immune spleen cells is much lower in NZB than in DBA/2 recipients. Immune spleen cells from DBA/2 donors do not provide more effective suppression than NZB spleen cells in NZB recipients. Conversely, immune spleen cells from NZB donors strongly suppress the anti-SRBC primary response of DBA/2 recipients to the same extent as DBA/2 immune spleen cells. Finally, NZB mice generate specific suppressor cells but their primary antibody response is not sensitive to this suppressor activity.

Animals↗