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Biomedical subjects

G Janossy

Publications and source records attributed to G Janossy.

At least 163 records · Page 9Linked to original sources
PubMed1986

T lymphocyte regeneration after transplantation of T cell depleted allogeneic bone marrow.

The regeneration of T cell subsets was studied with double immunofluorescence marker methods in 37 patients who received HLA matched T lymphocyte depleted bone marrow transplants (BMT) as part of the treatment for their haematological disease. A cocktail of anti-pan-T (CD6: MBG6) and anti-suppressor/cytotoxic-T cell (CD8: RFT8) monoclonal antibodies was used with rabbit serum as a source of cytolytic complement to achieve selective T cell lysis. The T8+ cells reached low normal values around 60 days post-transplant and remained within the normal range throughout the study (greater than 150 days). This observation is in contrast to our previously published results in patients who, after receiving BMT without efficient T cell depletion, had increased numbers of circulation T8+ cells from 60 days post-transplant. In the present study Leu-7+, RFT8- cells reached normal values rapidly but the reconstitution of T4+ lymphocytes was slow: low normal levels were reached only around day 150 following BMT. The degree of graft-versus-host disease (GVHD) seemed to be related to the number of residual T cells infused: two of the three patients who received the highest numbers of T cells developed Grade II III; otherwise GVHD was minimal. Among the clinical parameters studied cytomegalovirus (CMV) immune status moderately influenced reconstitution: at 55-90 days post-transplant T8+ cells were present at the upper normal levels in seven out of 15 patients receiving BMT from CMV seronegative donors, but in none of the 16 individuals receiving BMT from seropositive donors. CMV related complications were relatively uncommon. Thus the most significant factor in preventing 'T8+ cell overshoot' and T cell imbalance during regeneration appears to be the depletion of T (including T8+) lymphocytes from marrow. The differences of T8+ cell reconstitution in this and previous studies may reflect a different regeneration pattern from T cell precursors as opposed to inoculated mature T cells.

Adolescent↗
PubMed1986

Studies on human prothymocytes by means of an agar T-cell colony assay.

The identity of bone marrow (BM) T colony-forming cells has led to controversy because of BM contamination with mature T cells having clonogenic potential. To circumvent this problem, extensive purging of BM cells was achieved, using E-rosetting and complement-dependent cytotoxicity, with a cocktail of monoclonal antibodies (Mabs): CD6 + CD8 + CD4 + CD2 and two successive rabbit Complement (C) treatments. This resulted in a 2-log elimination of mature T cells, as assessed by marker studies. T-cell-depleted marrow (TDBM) was plated in agar in the presence of PHA- and B+ null cell-derived prothymocyte differentiating activity (PTDA). Two peaks of colony formation were observed on days 7 and 10 of incubation. Both seven- and ten-day colonies contained mainly T4+ and only a few T8+ cells, which also expressed T3, T11, HLA-DR, and Tac antigens. These colony-forming cells were enriched (three- to fourfold) by discontinuous Percoll gradient centrifugation. These results point to the existence of marrow T-cell progenitors, which differ in their kinetics of colony generation and surface markers.

Agar↗
PubMed1986

Leukemia diagnosis and testing of complement-fixing antibodies for bone marrow purging in acute lymphoid leukemia.

In this paper a microplate method is described for diagnosing acute leukemia and for investigating the reactivity of monoclonal antibodies (MoAbs) against membrane antigens in combination with rabbit or murine antibodies to nuclear terminal transferase (TdT). The speed of this method facilitates the investigation of fresh leukemic cells from individual patients and assesses the cytolytic efficacy of the relevant MoAbs in the presence of complement (C'). Lymphoblasts (TdT+) are mixed in equal proportions with known numbers of "inert" cells, eg, RBC or nonleukemic bone marrow (BM). Following incubation with MoAbs and C' the ratio of residual TdT+ cells and inert cells is determined on cytospin preparations. Initially, percentages of TdT+ cells are counted in a unit volume of 5,000 inert cells, followed by the scanning of greater than 2 X 10(4) inert cells on entire slides. With this method more than 4 log cytoreduction of TdT + cells is detected. The method is also applicable for studying the cytolysis of malignant B cells by using mostly monoclonal lg expression rather than TdT for the identification of residual B cells. Ten representative patients selected from a group of greater than 100 are reported. In some cases cytoreduction of greater than 4 log with no identifiable residual TdT + cells is achieved by a single C'-fixing MoAb: anti-CD10 (RFAL3) in common acute lymphoid leukemia (ALL) and anti-CD7 (RFT2) in T cell ALL (T-ALL). Other cases require cocktails of anti-CD10, anti-CD19, and anti-CD24 in common ALL or anti-CD7 and anti-CD8 in T-ALL. In T-ALL a few TdT + cells remain that exhibit the features of normal TdT + BM cells (CD7-, HLA-DR+). This is particularly noticeable when patients are studied in partial remission or if nonleukemic BM is used as a source of inert cells. The methods described here contribute to establishing a range of MoAbs (ie, of IgM class) and techniques for efficient purging and to comparing the efficacy of "clean-up," in remission, of common ALL, T-ALL, and B cell malignancies.

Antibodies, Monoclonal↗
PubMed1985

Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia.

Using a sensitive immunohistochemical technique and a specific monoclonal antibody (RFD-3), follicular dendritic cells (FDC) have been demonstrated in a significant proportion (6/12) of bone marrow samples from patients with nodular marrow involvement of B-cell chronic lymphocytic leukemia (B-CLL). In all cases with "packed marrow" involvement and advanced stages of disease the FDC were absent. As these accessory cells are normally present only in the lymph nodes, their presence in the bone marrow is in accord with the view that B-CLL might be the malignancy of an immature subpopulation of lymph node lymphocytes that invade the bone marrow.

Adult↗
PubMed1985

A rheumatoid arthritis B cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia.

An abnormal subpopulation of B cells expressing the T1 antigen, which is normally restricted to T cells, was demonstrated in the peripheral blood of 16 patients with rheumatoid arthritis. This T1+ B cell population accounted for a mean of 19.6% (upper limit 48%) of the circulating B cells and did not correlate with clinical disease activity, rheumatoid factor, or drug treatment. The highest percentage of T1+ B cells found in the blood of 8 patients with connective tissue diseases, including systemic lupus erythematosus, was 5% of the B cells, and for normal controls, it was was 3% of the B cells. As previously reported, we confirmed that the T1+,Ig+ phenotype was a feature of leukemic cells in B-type chronic lymphocytic leukemia. The finding of increased numbers of T1+ B cells in patients with rheumatoid arthritis and those with B-type chronic lymphocytic leukemia raises the possibility that these cells play a role in a spectrum of diseases, including those involving autoimmunity and malignancy.

Antibodies, Monoclonal↗
PubMed1985

Relationships between blood product exposure and immunological abnormalities in English haemophiliacs.

Amongst 160 English haemophiliacs treated with clotting factor concentrates, abnormalities of T lymphocyte subset distribution (characterized by low T4/T8 ratios and high total T8 counts), low in vitro phytohaemagglutinin stimulation and raised serum IgG levels, were more common in patients with haemophilia A than B, in patients who had received heavier blood product exposure, and in adults rather than children. A slight reduction in lymphocyte and platelet counts was found in 26% and 17% of patients. In the sample of patients tested, serum alpha 1-thymosin levels were often raised, but beta 2-microglobulin levels were usually normal. Fractionation procedures used to prepare clotting factor concentrates, and the amounts of concentrate used, are more likely to be causally related to these immunological abnormalities than the origins of source donor plasmas.

Adolescent↗
PubMed1985

Activated T lymphocytes of the synovial membrane in rheumatoid arthritis and other arthropathies.

Immunohistological techniques were used to identify activated T lymphocytes within the synovial membrane of patients with rheumatoid arthritis, using the monoclonal antibody (MoAb) RFT2, which identifies a 40-k dalton molecule preferentially expressed by T blasts or activated cells. Using this reagent together with a monoclonal 'cocktail' that stains all T cells, cell counts on consecutive sections of rheumatoid synovium revealed that up to 50% T lymphocytes were RFT2+ (range 9.3-50.2%, mean 25.4). Subsequent analysis using combination immunofluorescence demonstrated that over 90% of these activated cells were of the T4+ subset. Furthermore all these cells appeared to be Leu8-, suggesting that the activated population were exclusively 'true helpers' and not suppressor inducers. Studies indicated that 50% of the RFT2+ cells were positive with anti-Tac MoAb. Comparisons with tissues from other arthropathies demonstrated that this relatively high proportion of RFT2+ cells was a feature restricted to rheumatoid arthritis, although biopsies from patients with psoriatic arthritis and ankylosing spondylitis also contained activated cells. Biopsies of Reiter's syndrome, osteo-arthritis, and pigmented villonodular synovitis contained no activated cells, nor were any seen in sections of normal synovium. The presence in rheumatoid synovial membrane of activated T cells which are only of the T4+, Leu8- subset adds weight to the suggestion that local immunoregulatory dysfunction contributes to the chronic inflammation of rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1985

Expression of the common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease.

Expression of the gp100 common acute lymphoblastic leukaemia antigen (CALLA) was studied in the mucosa of the gut by means of indirect immunofluorescence on cryostat tissue sections with a panel of eight monoclonal antibodies to common acute lymphoblastic leukaemia antigen (anti-CALLA antibodies) and two antibodies to non-CALLA leukaemic antigens. Expression of CALLA was absent from normal stomach epithelium, adult and fetal colonic epithelium of normal histology, and colonic epithelium from patients with Crohn's disease or ulcerative colitis. By contrast, all eight anti-CALLA antibodies gave a characteristic reaction in normal adult and fetal small bowel mucosa, with specific localisation to the entire brush border of jejunal epithelium. Whereas seven of these antibodies reacted both with normal jejunal epithelium and with the damaged epithelium of patients with coeliac disease, antibody RFAL-2 reacted strongly only with histologically normal small bowel but more weakly in patients with coeliac disease to a degree related to the amount of histological abnormality. Expression of the moeity like CALLA identified with RFAL-2 was strongest in crypt epithelium and proportionally diminished along the villi according to the amount of histological damage in coeliac disease, being essentially absent in patients with "subtotal villous atrophy."

Adult↗
PubMed1985

Immunohistological analysis of lung tissue from patients with cryptogenic fibrosing alveolitis suggesting local expression of immune hypersensitivity.

Immunohistological analysis using monoclonal antibodies in conjunction with histochemical techniques has been applied to lung biopsy material from patients with cryptogenic fibrosing alveolitis. Subsets of lymphoid and non-lymphoid cells have been identified in situ. This analysis showed that the inflammatory cells present were predominantly mononuclear. Most of the lymphoid cells were B lymphocytes, organised into follicles with occasional germinal centre formation. IgM was the major class of immunoglobulin expressed. Both T4+ and T8+ lymphocytes were seen diffusely distributed in the interstitium. The T4+ positive cells were also seen within the B lymphoid follicles. Almost all non-lymphoid cells expressed the phenotype of inflammatory macrophages, but a few also expressed a phenotype characteristic of interdigitating cells. These results suggest that a local B lymphoid immune response is occurring in cryptogenic fibrosing alveolitis. The possibility that a cell mediated immune response is also emerging is discussed.

Adult↗
PubMed1985

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Adult↗
PubMed1985

The microenvironment of coeliac disease: T cell phenotypes and expression of the T2 'T blast' antigen by small bowel lymphocytes.

Peroral jejunal biopsies were studied by double-label immunofluorescence on cryostat tissue sections from control patients of normal histology and patients with coeliac disease. A panel of monoclonal antibodies was used to identify T cells and T cell subsets, together with antibody markers of cell stimulation (the T2 40 kdalton T blast specificity), proliferation (T9 and Ki67) and activation (HLA-DR and Ig receptors). In normal mucosa, expression of T2 was predominantly found in the T8+ intraepithelial cytotoxic/suppressor population. In coeliac disease there was little alteration of T4:T8 ratios per se, but a much higher percentage of T8-T4+ helper/inducer cells expressed the T2 antigen (approx. 30% compared to approx. 10%), manifest as an accretion of T2+T8- cells in the epithelium and subjacent stroma. Additionally, T cell lymphoid aggregates were observed in the lamina propria, consisting of greater than 90% T4+ cells, of which the majority (60-80%) were also T2+. The increase of stimulated helper cells correlated well with the pathology of coeliac disease, being most marked in untreated cases of maximal tissue damage, and least in well treated cases with restoration of normal morphology. By contrast, an increased tendency for the T8+ cells to co-express T1 in untreated coeliac disease was not observed in treated disease, even in cases where failure to adhere to a strict gluten free diet had resulted in little histological improvement. There was little evidence of T cell activation or proliferation. The observation that T helper cells undergo migration and stimulation suggests an imbalance in immunoregulation which causes a breakdown of normal immune tolerance to dietary gluten, and therefore may be a crucial mechanism of tissue damage in coeliac disease.

Adolescent↗
PubMed1985

Human B cell development. II. Subpopulations in the human fetus.

In man, during fetal development the B cell populations show distinct phenotypes at different tissue sites. The pre-B and B lymphocytes of the fetal liver and bone marrow express IgM and B cell markers, B1 (CD20) and BA-1 (CD24). These "early" cells are negative with a number of other reagents, anti-IgD, RFB4 (CD22), RFB6 (CD21), and RFA-2, which on the other hand recognize peripheral B cells. These peripheral B lymphocytes in the developing fetus are heterogeneous. The diffusely distributed B cells in the earliest lymph node samples, 16 to 17 wk of gestational age, and from 16 to 21 wk in the spleen, are strongly IgM+ (IgD+,RFB4+,RFB6+, and RFA-2+) but lack T cell-associated markers such as T1 (CD5, p 67,000 dalton equivalent of murine Ly-1) and Tü-33. In fetal lymph nodes, primary nodules develop around the follicular dendritic (FD) cells from 17 wk onward, and contain a virtually pure population of B cells; B1+,BA1+,RFB4+,RFB6+,RFA-2+, which simultaneously express IgM,IgD together with T1 (CD5), a T cell-associated antigen. A sizeable subpopulation of these IgM+,T1+ cells are also positive for Tü-33, another T cell-associated marker. In the spleen, the B cells of the IgM+,IgD+,T1+ type appear in smaller numbers and only relatively late around wk 22. These cells are diffusely distributed at first, and start accumulating around the small FD cell clusters as soon as these emerge about the 23rd gestational wk. At that time, the IgM+,T1+B cells can also be washed out from the peritoneal and pleural cavities. The T1+,IgM+B cells may represent the normal equivalent cells of B chronic lymphoid leukemia and centrocytic lymphoma, and appear to be the counterpart of Ly-1+,IgM+B cells in the mouse.

Adult↗
PubMed1985

Microenvironments in the normal thymus and the thymus in myasthenia gravis.

The disposition of epithelial cells and extracellular matrix, in the thymus of 8 cases of myasthenia gravis (MG) and in controls (over a wide age range) was studied. In the controls, the subcapsular epithelium was strongly Leu-7-positive in the fetus, negative in childhood, and positive again in adults. Another antibody, RFD4, also labeled the subcapsular epithelium in childhood and adults, but not fetal samples. The samples from MG cases showed the same staining pattern as adult control samples. The medullary epithelium was also RFD4+, and at all ages. The most striking changes in the advanced cases of MG were the unusual arrangement and hypertrophic appearance of medullary epithelial cell areas, separated by laminin-positive basement membranes from the alternating multiple bands of peripheral lymph-node-like areas. The latter had regions resembling the paracortex of lymph nodes as well as germinal centers (GCs). The T-cell zones contained heavy deposits of fibronectin. These T-cell zones were unique to the thymus in MG and were absent in the two normal thymic samples with isolated GCs. In MG the laminin-containing basement membrane, which separated the medullary epithelial and peripheral lymph-node-like areas, was fenestrated at circumscribed points closest to the GCs, thus apparently permitting communication among the medullary epithelium, the T-cell zones, the GCs and the associated antigen-presenting cells. Large numbers of interdigitating cells and some lymphocytes of cortical thymocyte phenotype were also found at these special sites, where opportunities for autosensitization may persist in MG.

Adult↗