Evidence for reduced erythroid burst (BFUE) promoting function of T lymphocytes in the pure red cell aplasia of chronic lymphocytic leukemia.

T cells stimulate the proliferation of BFUE (burst forming units-erythroid) from normal blood null cells in an in vitro culture system in the presence of erythropoietin. To determine whether abnormal BFUE proliferating effect of T cells could explain the pure red cell aplasia in chronic lymphocytic leukemia (CLL-PRCA), we investigated the erythropoietic function of T and null cells in four patients with CLL-PRCA and compared results to three patients with idiopathic pure red cell aplasia (I-PRCA) and normals. Sera from I-PRCA patients (P greater than 0.05) but not CLL-PRCA patients (P less than 0.1) inhibited erythroid stem cell proliferation in the presence of complement. BFUE in null cells of all PRCA patients were barely detectable or absent (P less than 0.0025). Normal or I-PRCA T cells increased BFUE proliferation from PRCA null cells of six patients (P less than 0.001). In contrast, CLL-PRCA T cells were poor stimulators of BFUE from autologous (P less than 0.001) or allogeneic null cells (P less than 0.02). Treatment with cyclophosphamide and prednisone induced reticulocytosis in all four CLL-PRCA patients. After treatment, in two cases, the burst promoting function of T lymphocytes was normal. Analysis of T cell subpopulations in two CLL-PRCA patients, suggested that the reduced burst promoting function was due to decreased numbers and/or function of T cells bearing Fc receptors for IgM (TM cells). These findings suggest that reduced generation of a burst promoting activity by CLL-PRCA T cells may contribute to the pathogenesis of PRCA in chronic lymphocytic leukemia.

Normal T-lymphocyte function in psoriatic patients undergoing methoxsalen photochemotherapy.

Peripheral blood lymphocytes from psoriatic patients undergoing photochemotherapy using oral 8-methoxypsoralen and high-intensity long-wave ultraviolet radiation, were isolated and their ability to respond to phytohemagglutinin and to form spontaneous rosettes with sheep red blood cells was measured in vitro. Seventeen patients were investigated who had received 200 to 3700 Joules/cm2 of ultraviolet radiation over a 6- to 33-month period. No significant defects in lymphocyte blastogenesis or E-rosette formation were detected in these patients.

Hydrogen peroxide-mediated inhibition of T-cell response to mitogens is a result of direct action on T cells.

Hydrogen peroxide, a reactive oxygen intermediate produced by activated neutrophils, has been shown to inhibit the response of human T lymphocytes to mitogens and alloantigens. Since hydrogen peroxide is known to react with iron and to induce lipid peroxidation, we compared the effects of hydrogen peroxide and a lipid peroxidation product, malondialdehyde, on the response of human peripheral blood mononuclear cells to T-cell mitogens. Peripheral blood mononuclear cells pretreated with 1 mmol/L of malondialdehyde, washed, and resuspended in fresh medium exhibited no inhibition of phytohemagglutinin responsiveness. Peripheral blood mononuclear cells treated in the same manner but with 200 mumol/L of hydrogen peroxide were inhibited by more than 95%. The addition of ferric edetate did not alter the inhibitory effects of 50 to 100 mumol/L of hydrogen peroxide, nor did the addition of deferoxamine, an iron chelator. These studies suggest that exogenous lipid peroxidation does not affect lymphocyte activation but that hydrogen peroxide has a direct inhibitory effect. Although monocytes are necessary for T-cell mitogenic responses, the effect of hydrogen peroxide was found to be directed at T lymphocytes. Exposure of T cells to a single dose of 200 mumol/L of hydrogen peroxide resulted in more than 71% suppression of the proliferative response measured 48 hours later, but the effect was spontaneously reversed by 72 to 96 hours. Repeated exposure of the cells to hydrogen peroxide resulted in continued inhibition of the proliferative response. These findings suggest that hydrogen peroxide produced by inflammatory phagocytic cells might be capable of suppressing the immune response of nearby T lymphocytes.

Adherence of multiple sclerosis lymphocytes to measles infected cells.

Adherence of lymphocytes from multiple sclerosis (MS) patients and control subjects to cells persistently infected by measles and control cells was studied. No statistically significant difference between MS patients and controls could be found in this test. Lymphocytes adhered more readily to cells infected by measles than to control cells. The cell to cell contacts are made by the tips of the microvillii of the Lu cells.

Proportional and functional studies of the infiltrating lymphocytes in the parotid gland of Sjögren's syndrome associated with rheumatoid arthritis.

Lymphocyte subpopulations and functions were examined in the salivary (parotid) gland lymphocytes (SGL) obtained as a cell suspension from a patient with Sjögren's syndrome associated with rheumatoid arthritis, in comparison with peripheral blood lymphocytes (PBL). Serial studies on the lymphocyte subsets in PBL using monoclonal antibodies to helper or suppressor T cell subsets (OKT4 or OKT8) demonstrated a decreased proportion of the OKT8 subset (OKT4/OKT8 ratio: 7.1-34.0). Major infiltrating cells in the gland were surface immunoglobulin-bearing B cells, and 23-35% of the SGL were T cells by both the E-rosetting method and OKT3-monoclonal antibody reactivity. Moreover, OKT4/OKT8 ratios were definitely lower in the SGL (1.0 and 1.7) than those in the PBL of the patient. Mitogen-induced lymphocyte proliferative responses of the SGL were markedly diminished, although the possible participation of defective macrophages was considered. The autologous mixed lymphocyte reaction was low in both PBL and SGL. PBL of the patient showed normal proliferative responses to mitogens except for PWM stimulation. Suppressor effects of the SGL for the proliferative responses of autologous and allogeneic PBL were demonstrated. Con A-induced suppressor function was inducible in the SGL, whereas that function could not be demonstrated in the patient's PBL.

T cell leukaemia in the rat: the pathophysiology.

A new transplantable lymphocytic leukaemia of the inbred Hooded Oxford strain of rat is described. Fewer than 10 cells will transfer to syngeneic recipients. Leukaemic cells bear the surface markers of thymus-derived (T) cells and recirculate from blood to lymph. In contrast to the usual thymic lymphomas of rodents the pathophysiology of the disease bears a close resemblance to human acute lymphoblastic leukaemia.

T-Cell hydrids: I. Selection of thymidine kinase deficient subline EL-4R from EL-4 cell population.

Thymidine kinase deficient (TK-) cell line EL-4R suitable for production of T-cell hybrids has been selected from the EL-4 cell population by treatment with 5-bromodeoxyuridine. Comparison of the EL-4 and EL-4R cell lines revealed differences in chromosome constitution and electrophoretic mobility of both cell populations. Both, EL-4 and EL-4R cells had a modal number of 39 chromosomes; the percentage of cells with modal number of chromosomes and the percentage of biarmed chromosomes in the EL-4R line was higher than that of the EL-4 line. Anodic electrophoretic mobility of EL-4R cell population was faster than that of EL-4 cells, respective mean values being 0.96 and 0.91 X 10(-4) cm2 s-1 V-1.

Spontaneous familial systemic lupus erythematosus in a canine breeding colony.

A colony of German shepherd dogs was studied in which a high proportion of antinuclear antibody (ANAb) carriers and dogs with systemic lupus erythematosus (SLE)-like signs were found. The titre of serum thymulin and the percentage of circulating T lymphocytes were both low. The incidence of disease decreased down the generations through the introduction of outside sires, thus suggesting a genetic origin for the disease.

[AIDS: epidemiology, physiopathology and clinical aspects]. / AIDS: note di epidemiologia, fisiopatologia e clinica.

The epidemiology, physiopathology and clinical aspects of adult and paediatric AIDS (Acquired Immune Deficiency Syndrome) are discussed and recent bibliographical references are reported.

[Study of T lymphocyte subpopulations in patients with leprosy, using incubation with theophylline]. / Estudio de subpoblaciones de linfocitos T en pacientes con lepra, mediante la incubación con teofilina.

T cells and the theophylline resistant cells (the-r, helper cells) in peripheral blood of patients with different forms of leprosy were studied. Active lepromatous patients (LL+) showed a significant decrease in T lymphocytes and the-r cells. Nevertheless, in LL+ developing a reactional episode of erythema nodosum (LL-ENL) a restoration in the level of the-r cells was observed. It is concluded that in LL+ patients the depression of T cells and the-r cells represents an imbalance in the T-T cellular cooperation with a defective cellular immune response. On the other hand, the recovery of the-r cells in LL-ENL support the hypothesis of a cell mediated immune mechanism in the immunopathology of this reactional episode.

Increased proliferation of T lymphocytes in the blood of patients with Hodgkin's disease.

We investigated the number of DNA-synthesizing T lymphocytes in the blood of patients with Hodgkin's disease, with infectious mononucleosis and in normal controls. T cells were characterized by their ability to form rosettes with unsensitized neuramidase-treated sheep red blood cells. Cells in DNA synthesis were evaluated autoradiographically after in vitro incubation with [3H]thymidine. Our results indicated a preferential proliferation of T lymphocytes in the blood of patients with Hodgkin's disease and infectious mononucleosis and suggested an increased turnover of these cells.

[T lymphocytes functions in mercuric chloride-induced membranous glomerulonephritis in man. Evidence for a defect of presentation of the histocompatibility class II molecules at the cell surface (author's transl)]. / Fonctions lymphocytaires T au cours d'une glomérulonéphrite extramembraneuse induite par une intoxication chronique au mercure.

Membranous glomerulonephritis (MGN) is one of the well documented manifestations of autoimmunity during chronic mercuric chloride (HgCl2) intoxication. We have carried out immunological investigation of the T cell functions in a patient presenting an HgC12-induced MGN. Circulating auto-antibodies and immune complexes were absent from the serum. Lymphocyte transformation with HgCl2 over a wide range of doses (10(-3) to 10(-8) M) was negative. E rosettes, mitogen reactivity, allogeneic reactivity evidenced by a one way mixed lymphocyte culture gave slightly diminished results. These findings contrasted with a severe impairment of the stimulative ability of lymphocytes. This defect might be related to the inability of D, DR products to be exposed at the cell surface and impeding the allogeneic recognition by foreign lymphocytes. This lymphocyte defect in the course of an HgC12 MGN in man would be correlated with lymphocyte abnormalities found in experimental HgC12-treated rats. The results of this study would favour the hypothesis of a direct role of HgC12 on lymphocyte rather than a direct action on glomerular basement membrane.

Induction of T cell-independent eosinophilia in mice with polymyxin B and schistosome infection.

This study examined the elevation of blood eosinophil counts in athymic and thymus-intact mice after repeated injections of polymyxin B with and without infection by Schistosoma mansoni. In athymic mice, a modest, comparable eosinophilia occurred after polymyxin B injection or parasite infection alone, or after a combination of both. In thymus-intact mice, polymyxin B injection caused a similar low grade eosinophilia, and schistosome infection produced a much higher level of eosinophilia. The combination resulted in the highest levels during the early weeks after infection; this hyperresponsive phenomenon was most apparent following 5 to 7 weekly polymyxin B injections, and the total eosinophil count approximated that derived by adding the eosinophil counts induced by polymyxin B injections or schistosome infection alone. In spite of the changes in blood eosinophil counts, tissue eosinophilia in the liver revealed no apparent differences. Furthermore, in schistosome-infected and polymyxin B-injected thymus-intact mice, hepatic granulomas reached a maximal size earlier than in mice that were only infected, and there was an over-all reduction in mast cell counts. The findings indicate that a T cell-independent eosinophilia occurs under a variety of circumstances. In athymic mice, it accounts for all peripheral eosinophilia, whereas in thymus-intact mice, it operates independently from the well known T cell-dependent eosinophilia of parasite infections.

The role of viral transformation and cytogenetic changes in viral oncogenesis.

A wide variety of DNA viruses and a more restricted family of RNA viruses can transform normal cells in vitro. Transformation means either immortalization and/or the appearance of certain phenotypic changes. Although it has been often inferred that in vitro transformation can be essentially equated with malignant transformation, increasing evidence indicates that the latter, reflected by tumorigenicity in vivo, requires additional cytogenetic changes. The evidence will be reviewed for EB virus-associated human malignancy (Burkitt's lymphoma) and the role of the 14q + translocation marker in human B-cell neoplasia. These findings point to an initiating role of viral transformation, reflected by in vitro immortalization, followed by a cytogenetic evolution where chromosome 14-associated changes are essential for the liberation of B lymphocytes from super-imposed controls. The contrast of tissue-associated, specific chromosomal changes that bring about malignant transformation after the initiating impact of different agents will be illustrated experimentally for murine T-cell lymphoma. Here, X-ray, DMBA and different virus (RadLV, Gross virus)-induced T lymphomas show the same chromosomal change: trisomy 15. It may be questioned whether viral transformation can ever lead to neoplasia in the absence of subsequent cytogenetic changes.

Kinetic studies on lymphocytes labelled with indium 111-oxine in patients with chronic lymphocytic leukaemia.

The kinetics of 111Indium-oxine-labelled autologous blood lymphocytes were studied in normal subjects and 10 patients with chronic lymphocytic leukaemia (CLL). In both normal and leukaemic subjects, intravascular survival of lymphocytes was characterized by two exponential decreases, the first being a rapid one and the second slow phase. T 1/2 of the second phase for normal T lymphocytes (52.0 +/- 3.2 h: mean +/- SEM) was longer than that for B lymphocytes (31.6 +/- 2.8 h). T 1/2 of the second phase in patients with CLL was 15.1 to 192.6 h, which correlated well with the clinical stage of CLL by the Rai classification. Body surface scanning revealed prominent splenic accumulation of labelled cells in normal individuals and patients with CLL. Lymph node visualization was recognized in all patients with T-cell CLL; however, there was no visualization in 8 of the 9 patients with B-cell CLL. The longer survival time and splenic and lymph node visualization suggest that an expansion of the extravascular lymphocyte pool may be important in the pathophysiology of CLL.

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.

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma of the skin. A morphological, immunophenotypical, and ultrastructural study of two typical cases.

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma are recently defined lymphoma types that both occur in the skin. This report outlines the characteristics of these lymphomas and describes the clinical, histological, immunological, and ultrastructural features as seen in two typical case histories. Cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome are heterogeneous; they deserve further scientific attention to obtain data about their natural history and their response to therapy.

Serum thymic hormone thymulin activity is normal in children with asthma.

In asthma, it has been hypothesized that suppressor T-lymphocytes play a protective role and have been reported to be functionally abnormal. Thymic hormone thymulin plays a role in the differentiation of T-lymphocytes and plasmatic thymulin concentration and is related to the functional state of the thymus. To assess the participation of the thymus in the impairment of T-lymphocyte function, we measured plasma thymulin activity in children with allergic asthma (N = 40). The plasma thymulin activity was compared with plasma thymulin activity of children with nonallergic asthma (N = 6), children with atopic dermatitis (N = 9) or allergic rhinitis (N = 7), and in age-matched healthy control children (N = 18) (age range of children studied, 2 to 19 years). Thymulin activity was found within the normal range (1/16 to 1/64) in all control children and in all children with allergic asthma and allergic rhinitis, as well as in all children with intrinsic asthma and atopic dermatitis. Our findings are at variance with the low thymulin activity previously reported in allergic asthma, and we could not explain these discrepancies. (Both studies used the same bioassay, and the population studied did not appear to be different.) T-lymphocyte abnormalities in subjects with asthma must be assessed by other means than measurement of thymic function.