Lymphocytes Of Healthy Controls Research Articles

High levels of bcl‐2 protein in circulating t lymphocytes, but not b lymphocytes, of patients with systemic lupus erythematosus

Defective regulation of programmed cell death (apoptosis) may play a role in the development of autoimmune diseases, and the proto-oncogene bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of bcl-2 in the peripheral lymphocytes of patients with systemic lupus erythematosus (SLE), a prototypical autoimmune disease. Levels of bcl-2 expression in the lymphocytes of patients with SLE and, for comparison, in the lymphocytes of healthy controls and patients with rheumatoid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2-color cytofluorography and RNA analysis. In SLE patients, a significant proportion of T cells expressed increased amounts of bcl-2 protein. By fluorescence-activated cell sorter analysis, bcl-2--enriched lymphocytes were found in the CD45RO+ as well as in the CD45RO-, and also in the CD4+ and CD8+, lymphocyte subpopulations. Mononuclear cells of patients with SLE showed increased amounts of bcl-2 messenger RNA. An increased percentage of strongly bcl-2 positive peripheral T lymphocytes was found in patients with bacterial infections, but not in those with RA. Although the occurrence of circulating T lymphocytes with abnormally high bcl-2 expression is not specific for SLE, it is evidence for a dysregulation of lymphocytic programmed cell death in this autoimmune disease.

Effect of morphine of adenylate cyclase activity in lymphocytes of healthy controls, alcoholics, and opiate addicts

Effect of morphine of adenylate cyclase activity in lymphocytes of healthy controls, alcoholics, and opiate addicts

Adrenergic control of circulating lymphocyte subpopulations. Effects of congestive heart failure, dynamic exercise, and terbutaline treatment.

The current studies were undertaken to explore the relationship between enhanced sympathetic nervous activity and lymphocyte subset distribution in three settings: congestive heart failure, dynamic exercise, and beta-adrenergic agonist treatment. We compared the number and subset distribution of circulating lymphocytes in 36 patients with congestive heart failure and 31 age-matched control subjects. The number of circulating lymphocytes was lower in heart failure than in control. This was due to a reduction in Tsuppressor/cytotoxic and natural killer cells without significant alteration of Thelper cells. The extent of the alteration was similar in patients with idiopathic and ischemic heart failure, but the reduction was more pronounced in patients with New York Heart Association class III-IV than in class I-II. The plasma catecholamine elevation in heart failure was also independent of etiology but more pronounced in the more severely ill patients. We also assessed lymphocyte subsets after acute stimulation of sympathetic activity by dynamic exercise and after treatment with the beta-adrenergic agonist terbutaline. Dynamic exercise until exhaustion increased the number of circulating lymphocytes in healthy controls and heart failure patients in a subset-selective manner. By contrast, a 7-d treatment with terbutaline caused a reduction in the circulating number of lymphocytes in some subsets that was identical to that seen in heart failure patients. We conclude that prolonged sympathetic activity reduces the number of circulating lymphocytes by a beta-adrenergic mechanism. Such alterations might be involved in the pathophysiology of heart failure and other disease states involving increased activity of the sympathetic nervous system.

A Diminished Adherence of Blood Lymphocytes of Patients with Thyroid Autoimmune Disease to High Endothelial Venules in the Thyroid and the Thyroid-Draining Lymph Nodes

The function of high endothelial venules (HEVs), present in the T-cell area of lymphoid tissue is to attract lymphocytes to secondary lymphoid organs ("homing"). In Graves' disease, sporadic goitre and lymphocytic thyroiditis HEVs develop in the thyroid. To study the "homing" of peripheral blood lymphocytes (PBL) of healthy individuals and thyroid patients to the thyroid area we studied the adherence of PBL of such individuals to HEVs present in Hashimoto's goitres and to HEVs in thyroid draining lymph nodes. A modification of the in vitro "homing assay" described by Stamper and Woodruff (J Exp Med 144: 823) was used. The number of PBL of patients with Graves' disease which adhered to thyroidal and thyroid-draining lymphnode HEVs was significantly (p less than or equal to 0.001, Wilcoxon test) less than that of healthy control PBL's; in the case of thyroid HEVs 12 (mean, sd 8, n = 18) patient lymphocytes adhered to 35 HEVs vs 19 (mean, sd 7, n = 16) healthy control lymphocytes; in the case of thyroid lymphnode HEVs 20 (mean, sd 12, n = 15) patient lymphocytes adhered vs 35 (mean, sd 9, n = 9) healthy control lymphocytes. PBL of a few sporadic goitre (n = 5) and atrophic lymphocytic thyroiditis (n = 2) patients also showed a diminished adherence to thyroidal HEVs. We also studied the homing capability of lymphocyte suspensions isolated from the thyroid glands of three Graves' disease patients; these infiltrated cells showed a normal adherence pattern to thyroidal HEVs. We favour the idea that the data should be explained by a redistribution of lymphocytes possessing "thyroid-specific-homing-receptors" from the circulation to the thyroid area in patients with thyroid autoimmune disease.

Detection of Activation Antigens on Chronic Lymphocytic Leukaemia Cells.

The peripheral blood mononuclear cells of patients with chronic lymphocytic leukaemia were characterized by the presence of a variety of cell surface differentiation antigens. The cells of 20 patients were found to be of B-cell phenotype when studied with antibodies directed against CD19, CD20, HLA-DR and sIg. Furthermore, a significant percentage of the cells gave a positive reaction with the monoclonal antibody to CD5. On the other hand, the CLL-cells did not express the CD21 antigen (C3d receptor, EBV receptor). We studied in parallel the presence of various activation antigens using 19 monoclonal antibodies grouped into 7 clusters (CD25, CD30, CD40, CD69, CD70, CD39, CD71). A significantly higher percentage of the CLL cells expressed activation antigens than lymphocytes from healthy controls. The percentage of CD3/HLA + DR + cells, compared to the healthy control lymphocytes was not increased in the CLL patients, and the activated cells in CLL were found to have characteristics of B-cells. Based on these results, we suggest that the CLL cells, like the cells in Hodgkin's disease and T-cell lymphoma, are not resting, but activated B-cells or the neoplastic abberrants of activated cells.

Analysis of variability in lymphocyte transformation tests

To estimate the importance of a number of variables influencing the results of the lymphocyte transformation test (LTT), we analysed retrospectively the results of 250 LTTs on healthy control lymphocytes tested during the last 5 years as part of the routine LTT program. Prospectively, frozen cells from 3 donors were tested together on 5 different occasions. Differences in day-to-day test conditions had only minor influence. The influence of biologic variables was also negligible. The 2 most important factors were intrinsic cell differences, most probably due to damage during freezing, and genetic influences. To demonstrate minor differences between donors or between bleeding dates, repeated testing is necessary to eliminate these intrinsic variables and to allow statistical analysis.

Effect of haemodialysis on the antibody-dependent and spontaneous cell-mediated cytotoxicity of patients with chronic renal failure

Antibody-dependent and spontaneous lymphocytotoxicity of blood mononuclear cells from 10 patients with chronic renal failure was studied before and after haemodialysis in xenogeneic chicken erythrocyte and allogeneic K-562 test systems. The originally impaired antibody-dependent and spontaneous lymphocytotoxicity of uraemic patients significantly improved following haemodialysis. Both pre- and post-haemodialysis uraemic sera strongly inhibited the antibody-dependent and spontaneous cytotoxicity of autologous and of healthy control lymphocytes.

ADHERENCE OF GLIADIN FRACTIONS TO LYMPHOCYTES IN COELIAC DISEASE

Mice were immunised with a mixture of low-molecular-weight peptides prepared from β-gliadin by digestion and ultrafiltration and found to be toxic to cultures of intestinal mucosa from patients with coeliac disease (CD). The antiserum obtained was used to detect the adherence of the same peptides to white blood cells of CD patients and healthy controls. 43% of B lymphocytes of CD patients exhibited binding of gliadin peptides compared with only 12·5% of their T lymphocytes and 17% of B lymphocytes of healthy controls. Adherence of gliadin fractions seemed to have no relation to the HLA antigens of the subjects. It is concluded that B lymphocytes of CD patients have a surface receptor for gliadin which may be important in the pathogenesis of CD.

Immunoglobulin- and complement-bearing lymphocytes in allergic contact dermatitis and atopic dermatitis (eczema).

SUMMARY The distribution pattern of immunoglobulin- or complement-bearing lymphocytes in healthy controls and in patients with contact dermatitis and with atopic dermatitis has been investigated. A significant predominance of IgD- and C3-bearing lymphocytes was found in ten patients with contact dermatitis. In atopic dermatitis patients the number of IgE- and to a lesser extent of C3-bearing lymphocytes was increased. The results indicate induction of stimulation of two distinct classes of immuno-logically competent lymphoid cell lines, one in contact and the other in atopic dermatitis. The increased number of B-cells in dermatitis indicates a decreased T-cell population and suggests a deficiency or disturbance of the recirculation of this population.