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Lymphocyte subset abnormalities in patients with spasmodic torticollis.

The aetiology of spasmodic torticollis is unknown but the patients form a heterogeneous group among which are cases apparently precipitated by a viral illness and others associated with autoimmune disease. We therefore decided to investigate the immunoregulatory lymphocyte subsets in our 11 cases. A significant decrease of both helper and suppressor lymphocytes was identified in the group, together with in vitro evidence of depressed suppressor cell function. Disturbance of the immune response may play a role in this puzzling disorder.

Adult↗

The effect of low-dose irradiation on unstimulated and PHA-stimulated human lymphocyte subsets.

A culture system was used to evaluate the radiosensitivity of CD4+ and CD8+ T cells, Leu 19+ cells, and B cells obtained from normal adult males. Unstimulated CD8+ lymphocytes (D0 = 55 cGy) were twice as radiosensitive as CD4+ cells (D0 = 115 cGy). B cells had an intermediate radiosensitivity (D0 = 100 cGy). Leu 19+ cells were much more radioresistant and expressed a D0 of 550 cGy. When lymphoid cells were irradiated 1 or 4 days before phytohemagglutinin (PHA) stimulation, they were more radiosensitive than if they were first stimulated with PHA and then irradiated. When lymphoid cells were irradiated 1 h after PHA stimulation each lymphocyte subset was characterized by an increase in the D0 to 150 cGy for B cells to 290 cGy for CD4+ cells, and to 240 cGy for CD8+ cells. In contrast, Leu 19+ cells exhibited a decrease in their D0 to 290 cGy after they were stimulated by PHA.

Adult↗

The effect of non-transferrin-bound iron on murine T lymphocyte subsets: analysis by clonal techniques.

A number of different immunological properties have been attributed to iron (Fe3+ and Fe2+) and iron-binding proteins. However, in many previous studies, high concentrations of iron were used and cell-cell interactions were not excluded as a possible cause of the observed immunomodulatory effects. In this study, clonal techniques have been used to examine the effect of non-transferrin-bound iron (Fe3+) on the T lymphocyte subsets required for the generation of cytotoxic T lymphocytes (CTL). Concentrations of non-transferrin-bound Fe3+ of 10 microM or greater were shown to inhibit the generation of C57, BALB/c and CBA allo-specific CTL in bulk culture. Limit-dilution analysis revealed that: (i) Fe3+ reduced the cloning efficiency of CTL-precursors (CTL-P) by up to 96% without affecting the rate of clone growth; (ii) Fe3+ did not affect the cloning efficiency of allo-stimulated Ly-2-ve T cell precursors but reduced the rate of clone growth of these cells; (iii) Fe3+ enhanced, by more than 13-fold, the function of clones of Concanavalin A (Con A)-induced suppressor T lymphocytes (STL) which suppressed in vitro the development of CTL from their precursor cells. The data provide further evidence that low concentrations of non-transferrin-bound Fe3+, of the same order as those reported to be present in the serum of patients with iron-overload, have significant immunoregulatory properties.

Animals↗

[T-lymphocyte subsets in peripheral blood and pleural effusion in tuberculous pleurisy and carcinomatous pleurisy: analysis by monoclonal antibodies].

By using monoclonal antibodies, OKT8(pant), OKT4(inducer/helper),OKT8(suppressor/cytotoxic) T-lymphocyte subsets were examined in 25 patients with tuberculous pleurisy and 15 patients with carcinomatous pleurisy. The results showed that percent and absolute counts of OKT8,OKT4,OKT8 in tuberculous pleural effusion were significantly higher than those in carcinomatous pleural effusion. Percent and absolute counts of OKT8, OKT4, in tuberculous pleural effusion were significantly higher than those in peripheral blood. OKT8% in peripheral blood of carcinomatous pleural effusion was significantly lower than that in peripheral blood of control group. When OKT8% greater than 65, OKT4% greater than 45, OKT8 number/mm8 greater than 1,000, OKT4 number/mm8 greater than 800, OKT8 number/mm8 greater than 500 in pleural effusion, it suggests pleural effusion is tuberculous. when OKT8% less than 55, OKT4% less than 45, OKT5 number/mm8 less than 500, OKT4 number/mm8 less than 300, OKT8 number/mm8 less than 200, it suggests pleural effusion is carcinomatous pleural effusion.

Adenocarcinoma↗

In situ analysis with monoclonal antibodies of lymphocyte subsets in myocardial biopsies from patients with dilated cardiomyopathy and idiopathic (viral) myocarditis.

This light- and electron-microscopic immunohistochemical study using monoclonal antibodies analyzes of the in situ lymphocyte subsets in endomyocardial biopsies from 11 patients with dilated cardiomyopathy (DCM) and three patients with idiopathic (viral) myocarditis (MYO). In the DCM patients both Leu 2a+ cytotoxic/suppressor T cells (Tc/s) and Leu 3+ helper/inducer T cells (Th/i) were identifiable in the myocardial lesions, and mean Th/i/Tc/s (T4/T8) ratio was 0.7 +/- 0.6 (mean +/- SD). In 9 of the 11 DCM patients, Tc/s were more numerous than Th/i cells, so the T4/T8 ratio was less than 1.0. On the other hand, the T4/T8 ratios varied widely in the three MYO patients; one of them had marked mononuclear cell infiltrates with many Th/i in the inflammatory foci and a T4/T8 ratio of 2.6. Immunoelectron microscopy revealed some Th/i in close contact with macrophages. These T cells in the myocardium of DCM and MYO patients appeared to be in vivo effector cells playing an important role in cell-mediated immune responses.

Adult↗

Two-color flow cytometry analysis of activated T-lymphocyte subsets in type I diabetes mellitus.

We addressed the question of whether newly diagnosed type I (insulin-dependent) diabetes mellitus patients showed an increased number of DR (la+) T-lymphocytes compared with nondiabetic siblings and normal control subjects. Two-color flow cytometry measurements of peripheral-blood lymphocytes showed a slight but statistically significant increase in DR+ T-lymphocytes in diabetic subjects as well as the nondiabetic sibling control compared with the normal control subjects. This difference was not present in long-term-diabetic subjects. Thus, in addition to minor changes in this lymphocyte subset in peripheral blood, the sibling data demonstrate a lack of specificity for the disease; therefore, these measurements are probably of limited diagnostic usefulness.

Adolescent↗

Improvement of cadaveric renal allograft survival by thoracic duct drainage: relation with T-lymphocyte subset modifications assessed by flow-cytometry.

Thoracic duct drainage (TDD) with reinfusion of cell-free lymph was performed in 118 prospective recipients within four months before transplantation. TDD was unsuccessful in 27 patients (A); it yielded 1-19 X 10(9) lymphocytes in 25 cases (B) and 20-185 X -10(9) in 66 cases (C). The incidence of acute rejection episodes and the requirement for early post-transplant dialysis were lower in C than in A. Six patients were studied for T-lymphocyte subsets, using monoclonal antibodies from OKT series and a monomorphic and HLA-DR (BL2) raised in our laboratory. During TDD peripheral blood lymphocyte (PBL) counts decreased and the percentage of BL2 cells increased. Simultaneously, typical small PBL were replaced by large less differentiated cells slightly labelled by OKT3, some of them bearing both OKT4 and OKT8 markers. The larger the depletion, the earlier the emergence of immature T-cells. In lymph fluid, lymphocyte counts decreased later than in blood, the proportion of T8+ cells lacking Fc receptors increased with time. Changes in B patients were less than in C. These results support the hypothesis that T-cell subset modifications represent the main immunological change accounting for better allograft prognosis.

Antibodies, Monoclonal↗

T-lymphocyte subsets in follicular lymphomas compared with those in non-neoplastic lymph nodes and tonsils.

Using monoclonal antibodies on frozen sections, the authors define the anatomic localization of T-lymphocyte subsets in follicular lymphomas as well as in nonneoplastic lymph nodes and tonsils. The percentage of Leu-1+ T cells in the follicles of follicular lymphomas (20 per cent) was virtually identical to that seen in the follicles of nonneoplastic lymph nodes or tonsils (22 per cent). There were 50 per cent T cells in the interfollicular regions of follicular lymphomas and 75 per cent in the paracortical regions of the nonneoplastic specimens. In neoplastic follicles the number of Leu-3a+ cells was 67 per cent of the number of Leu-1+ cells, whereas, virtually the entire T-cell population in the nonneoplastic follicles expressed the Leu-3a antigen. These T cells of helper phenotype may facilitate the neoplastic process or an immune response against it or may be bystanders to the B-cell proliferation. Hum Pathol 13:618-625, 1982

Antibodies, Monoclonal↗

Lymphocyte subsets and mitogen induced proliferation in adjuvant arthritis. Part II. Changes in function and numbers of lymph nodes T lymphocytes.

To evaluate the effects of lymphocytes on the pathogenesis of adjuvant arthritis (AA), the lymphocytic responses to phytohemagglutinin (PHA) and concanavalin A (Con A) and the percentages of T cell subpopulations were investigated in the inguinal lymph nodes of Long-Evans (LE) rats and Sprague-Dawley (SD) rats after a single injection of complete Freund's adjuvant. The response of LE to PHA increased to its maximum on the 14th day and correlated with the severity of AA. The responses of LE and SD rats to Con A were decreased on the 7th, 11th, and 14th days. Additionally, percentage of suppressor T cells of LE rats was lower than that of SD rats. Significant increases of percentage of helper T cells and of helper/suppressor T cell ratio were observed in LE rats, indicating a decrease or defect in the suppressor T cells in LE rats. In LE, we postulated that helper T cells are involved in the induction of AA, and a defect in the suppressor T cell function or numbers would subject LE to the development of AA. SD rats, on the other hand, with higher suppressor T cell numbers, were less susceptible to AA.

Animals↗

Differences between lymphocyte subsets of the cerebrospinal fluid in subacute sclerosing panencephalitis and acute aseptic meningitis.

In CSF of patients with acute aseptic meningitis (AAM) an increase in the percentage of total and active T lymphocytes was observed, whereas in SSPE a decrease in T cells was noted. In SSPE there was the increase in the relative number of lymphocytes bearing "avid" FcIgG receptor and decrease in alpha-naphthyl nonspecific esterase-positive cells, but in AAM the cell proportions were not disturbed. The changes in the peripheral blood lymphocytes subsets were less evident. The results seem to suggest that in AAM there is a strong T response in CSF with well preserved proportions of T-cell subsets, while in SSPE a low T-cell level may be accompanied by disturbances in T-cell function.

Acute Disease↗

[Levels of serum interleukin-15 and the expression of T-helper lymphocyte subsets in peripheral blood of children with juvenile rheumatoid arthritis].

OBJECTIVE: To study the changes of serum interleukin-15 (IL-15) levels and the expression of CD4(+)T (T-helper lymphocyte) subsets CD4(+)CD45RA(+) and CD4(+)CD45RO(+) in peripheral blood of children with juvenile rheumatoid arthritis (JRA). METHODS: The serum concentration of IL-15 was detected using ELISA in 39 children with JRA. The expressions of CD4(+)CD45RA(+)T and CD4(+)CD45RO(+)T in peripheral blood were detected by flow cytometry in 24 out of the 39 patients with JRA. Twenty-six age and sex-matched healthy children were used as the Control group. RESULTS: The mean serum IL-15 level in JRA patients was significantly higher than that in controls (1.37 +/- 0.98 pg/mL vs 0.96 +/- 0.41 pg/mL, P <0.05). Among the 39 JRA patients, the serum IL-15 level in 17 patients with systemic JRA increased remarkably (P < 0.01), but not in patients with the other two types of JRA, the oligoarthritis and polyarthritis (n=13, n=9, respectively), compared with that in controls. The mean serum IL-15 level of the JRA patients was significantly reduced after conventional treatment (P < 0.01). The serum IL-15 level in JRA patients positively correlated with white blood cell count (r=0.347, P <0.05) and C reactive protein (r=0.452, P < 0.01) but not with the erythrocyte sedimentation rate. The patients with high serum IL-15 levels (> or = medium level 1.73 pg/mL) had higher expression of CD4(+)CD45RO(+)T than those with low serum IL-15 levels (< medium level) (16.29 +/- 5.46% vs 11.75 +/- 3.15 %, P < 0.05). CONCLUSIONS: The serum IL-15 levels in JRA patients increased significantly. An increased IL-15 level can transform CD45RA into CD45RO in peripheral blood of patients with JRA, and then result in T lymphocyte activation and mediate the immunopathological impairment. IL-15 may be used a marker for the evaluation of severity of JRA.

Adolescent↗

Lymphocyte subsets in the peripheral blood of patients with multiple myeloma and benign monoclonal gammopathy.

A panel of monoclonal antibodies that identify various antigens present on T and B cells was used to characterize circulating blood lymphocyte subsets in multiple myeloma [(MM)--13 patients] and benign monoclonal gammopathy [(BMG)--5 patients]. In MM and BMG an increase in B cell proportions (BA 1 positive cells) was observed, whereas T cells (Lyt 3 positive cells) were reduced compared to normal controls. However, with respect to the T cell subset distribution, a marked diversity between MM and BMG was noted. This may help to differentiate BMG from MM. In MM a relative decrease in inducer/helper T cells (OKT 4 positive cells) and increase in suppressor/cytotoxic T cells (OKT 8 positive cells) as well as in NK/K T cells (Leu 7 positive cells) was observed. On the other hand, in BMG the relative T cell subset distribution was comparable to those seen in normal subjects.

Adult↗

[Lymphocyte subsets in bronchoalveolar lavage fluid from patients with idiopathic interstitial pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 15 patients with idiopathic interstitial pneumonia (IIP) and from 7 controls. Clinical criterial were used to divide the patients with IIP into two groups: acute (n = 5) and chronic (n = 10). Lymphocytes in the bronchoalveolar lavage fluid were analyzed with a flow-cytometric two-color system. Differential cell counts showed that percentages and numbers of lymphocytes were significantly higher in patients with acute IIP (44.2 +/- 25.2%, 12.3 +/- 8.18 x 10(4)/ml) than in controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4)/ml, p < 0.05) and in patients with chronic IIP (8.44 +/- 6.11%, 1.58 +/- 1.08 x 10(4)/ml, p < 0.05). In particular, percentages and numbers of CD8+ S6F1+ lymphocytes, which are regarded as activated cytotoxic T lymphocytes were markedly higher in patients with acute IIP (32.3 +/- 16.0%, 39.6 +/- 37.1 x 10(3)/ml), than in controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3)/ml, p < 0.05) and in patients with chronic IIP (10.6 +/- 6.16%, 1.88 +/- 1.42 x 10(3)/ml, p < 0.05). These data suggest that patients with acute IIP differ from those with chronic IIP in the percentage and the number of lymphocytes in bronchoalveolar lavage fluid, and that activated cytotoxic T lymphocytes may play an important role in the pathogenesis of acute IIP.

Acute Disease↗

Lymphocyte subset infiltration patterns and HLA antigen status in colorectal carcinomas and adenomas.

Fifty eight large bowel adenocarcinomas and 20 adenomas were studied immunohistochemically, using fresh frozen tissue sections, with regard to lymphocyte subpopulations (CD3, CD4, CD8, CD19, and CD20) in the inflammatory infiltrate and to expression of human leucocyte antigens (HLA-ABC, HLA-A2, and HLA-DR). The findings were related to differentiation and Duke's stage of carcinoma. The inflammatory infiltrate was found to have a phenotype that remained constant irrespective of the intensity of the inflammation. CD4 and CD3 positive cells predominated with fewer CD8 positive cells and a scanty diffuse CD19/20 positive cell population. CD19/20 follicular aggregates were common at the advancing margin of the carcinomas. There was no significant association with Duke's stage, differentiation or HLA status. HLA changes (ABC loss, A2 loss, and DR gain) were associated with differentiation, being more common and more extensive in poorly differentiated carcinomas. HLA-A2 loss was also associated with stage of progression of carcinoma. Inflammation associated with adenomas was found to have a similar phenotype to that associated with carcinomas. HLA changes in adenomas were uncommon, being seen in only one of our 20 cases.

Adenocarcinoma↗

[Quantitative variations of lymphocyte subsets in various kinds of cancer patients in the terminal stage].

Immunological studies of the peripheral blood were made in terminal breast cancer and terminal abdominal cancer patients. Two immunological parameters were studied: (1) lymphocyte subsets and (2) proliferative response to PHA. A decrease in the number of OKT-3(+) cells and an increase in that of OKT-8(+) cells were observed in abdominal cancer. It was suggested that the immunological status in abdominal cancer is more suppressive than in breast cancer. Increases in the number of OK-M1(+) cells and Leu-7(+) cells were observed in breast cancer. It is suggested that cytotoxic lymphocytes increase in number in breast cancer more than in abdominal cancer.

Breast Neoplasms↗

Lymphocyte subsets in primary sclerosing cholangitis.

As an initial step in testing the hypothesis that immunoregulatory abnormalities are important in the pathogenesis of primary sclerosing cholangitis, we determined the number and percentage of lymphocyte subsets in the peripheral blood of 33 patients with primary sclerosing cholangitis. In these patients, when compared with normal and diseased controls, there was a significant reduction in the total number of circulating T cells because of a disproportionate decrease in Leu-2a (suppressor/cytotoxic) cells. This decrease resulted in a significantly increased ratio of Leu-3a to Leu-2a cells. Patients with cirrhosis had significantly higher Leu-3a/Leu-2a (helper/suppressor) ratios than did noncirrhotic patients; both disease groups, however, had ratios that were significantly higher than controls. The number and percentage of B cells were significantly increased. Alterations in the percentage of B cells correlated significantly with histologic stage and concentrations of gamma globulin, serum IgG, and bilirubin. We conclude that these abnormalities are suggestive of a defect in immunoregulation in primary sclerosing cholangitis, which is not secondary to advanced liver disease alone and appears to be independent of chronic ulcerative colitis or obstructive jaundice.

Adult↗

Mouse T-lymphocyte activation by Urtica dioica agglutinin. I.--Delineation of two lymphocyte subsets.

Urtica dioica agglutinin (UDA) is a mouse T-lymphocyte-specific mitogen endowed with proliferative characteristics different from ConA, the prototypic T-lymphocyte mitogen. In particular, UDA induces 2-3-fold-reduced thymidine incorporation as compared to ConA. In an attempt to define the basis of this reduced proliferation, we analysed whether UDA binds to a unique subset of T lymphocytes or whether it activates only a T-cell subset. Cytofluorimetric analysis showed that this lectin binds uniformly to all T lymphocytes and does not, on this criterion, distinguish a particular T-cell subset. We next analysed whether UDA provokes the activation of all T lymphocytes. This was carried out by measuring the increase in cell size and the induction of the p55 chain of the IL2 receptor. The analysis showed that, throughout the kinetics of cell activation, only one subset of T lymphocytes increased in size and expressed the p55 chain of the IL2 receptor, suggesting that UDA activates only a subpopulation of T cells. This conclusion was strengthened by the analysis of 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA of UDA-activated cells. Two populations were easily identifiable: a BrdU-negative subset consisting of all the small p55-negative lymphocytes, and a BrdU-labelled subset including all the large p55-positive cells. BrdU was incorporated in both CD4+ and CD8+ cells, indicating that UDA did not distinguish helper from cytotoxic T lymphocytes. In addition to the p55 chain of the IL2R, all cycling cells expressed the Pgp-1 activation marker. The T lymphocytes, which bound UDA but did not proliferate, remained fully susceptible to subsequent stimulation by ConA. In conclusion, the capacity to proliferate upon UDA binding differentiates a UDA-sensitive from a UDA-refractory subset among splenic mouse T lymphocytes.

Animals↗

Identification of a new lymphocyte subset surface antigen, the expression of which disappears after in vitro and in vivo stimulation. Distribution, biochemistry, and functional studies.

Two monoclonal antibodies (MoAbs) are described (MD 2.6, IgG1 and MD 4.3, IgG2a) that react with a nonlineage specific lymphocyte subset surface antigen. This antigen is expressed on B cells, a subset of both T8+ and T4+ cells, cells that exert killer and natural killer cell activity in vitro, B cells in lymph nodes, and a small percentage of thymocytes. Expression of the antigen was found to be variable on T cells but not on B cells among individuals. Following polyclonal activation, expression of the determinant detected was lost from the cell surface. Both MD+ and MD+ cells responded to PHA and in MLC. MLC resulted in the generation of cytotoxic T lymphocytes and primed T lymphocytes in both the MD+ and MD+ subpopulations. In contrast, the response to soluble antigens was found to reside almost exclusively in the MD-subset. Immunoprecipitation indicates that the MoAbs react with an antigen that has a molecular weight of 220-240 KD which can be cleaved into subunits of 70-80 kD by beta-mercaptoethanol.

Antibodies, Monoclonal↗