Complement Receptor-bearing Lymphocytes Research Articles

Isolation and characterization of inflammatory cells from the human periapical granuloma.

Twelve histologically-confirmed periapical granulomas were evaluated by conventional immunologic rosette assays for the presence of T-lymphocytes and complement receptor-bearing lymphocytes. A technique for dispersing the granuloma cells into suspensions was adopted to facilitate performance of the assays which were not applicable to tissue sections. Differential cell counts by an acridine orange vital dye method disclosed that the cell suspensions contained 30% macrophages, 44% lymphocytes, 15% plasma cells, and 12% neutrophils. Complement receptor-bearing cells comprised 17.9%, and T cells comprised 34.5% of the unseparated inflammatory cells. This study provides the first direct evidence of a predominance of thymic-derived lymphocytes in the lymphocyte compartment of the periapical granuloma. Analysis of the data shows that cell-mediated immunity most likely plays a role in the pathogenesis of the periapical granuloma.

Cytomegalovirus encephalitis associated with thymoma and immunoglobulin deficiency

The clinical and immunologic findings in an elderly woman with thymoma and immunoglobulin deficiency in whom cytomegalovirus (CMV) encephalitis developed are described. The patient had absent serum immunoglobulins and no circulating immunoglobulin-bearing lymphocytes. Complement receptor-bearing lymphocytes were present in the peripheral blood, and circulating T lymphocyte numbers were within normal limits. She was anergic to a battery of skin test antigens, and her lymphocytes in vitro showed a selective unresponsiveness to CMV antigen while responding normally to phytohemagglutinin and streptokinase. The course of the encephalitis was progressive with quadriplegia, aphasia and coma developing within six months of onset of symptoms. This is the fifth reported case documenting an association between CMV infection and the syndrome of thymoma with immunoglobulin deficiency, but the first report of fatal CMV encephalitis in a patient with thymoma and immunoglobulin deficiency.

Effects of sulfasalazine on selected lymphocyte subpopulations in vivo and in vitro.

Sulfasalazine has proven to be an effective agent in the therapy of inflammatory bowel disease (IBD). Despite long and widespread usage, the mechanism of action of this drug is still not understood. Several investigators have suggested that the drug might act as an immunosuppressant. To examine this possibility, an in vivo study was undertaken to ascertain any quantitative change in the circulating T cells, Ig-bearing B cells, and complement receptor-bearing lymphocytes (CRL) of patients before and during therapy with sulfaslazine. Concomitant responses to skin test antigens were also evaluated. In vitro studies with control cells were performed to determine the influence of sulfasalazine and its components (sulfapyridine or 5-aminosalicylic acid) on the extent of antibody-dependent cellular cytotoxicity (ADCC), as well as on the number of T cells and CRL. Results indicate that neither sulfasalazine nor either of its components quantitatively alters those subpopulations of circulating mononuclear cells studied in vivo or in vitro--nor are these compounds responsible for any functional inhibition of ADCC.

Characterization of the Immunosuppressive State during Schistosoma Mansoni Infection

Abstract Analysis of a murine model of schistosomiasis revealed that both the thymus (T)- and bursa (B)-derived compartments of the immune system are modified during acute infection. The functional capacity of T and B lymphocytes to respond to mitogenic stimuli and the humoral response to thymus-dependent (SRBC) and thymus-independent (DNP-Ficoll) antigens are severely depressed. In addition, it was found that suppressor cells capable of inhibiting the response of normal lymphocytes to SRBC arise during acute infection. Although the splenic frequency of T (ϑ) and B (Ig+) cells remained constant during chronic infection, quantitative changes were detected in each population. In the T cell pool there was a decrease in the percentage of Ly-1+ cells and a concomitant increase in Ly-1+, 2+, 3+ cells, whereas the B cell pool showed a progressive loss of complement receptor-bearing lymphocytes, which apparently was the result of inactivation of surface complement receptor by a serum factor specifically found in infected mice. Characterization of the serum factor strongly suggests it is an immune complex. Thus, it appears that both suppressor cells and immune complexes contribute to changes noted in the immune system during acute schistosomiasis. Additional studies carried out in mice after unisexual infection revealed that egg production is not a necessary prerequisite for several of the immunologic phenomena associated with acute schistosomiasis.

Age-Related Changes in the Subsets and Functions of Human T Lymphocytes

Abstract The purpose of this study was to investigate changes in immunocompetence associated with aging in humans by the use of various immunologic parameters. Volunteers examined in this study were healthy or apparently healthy without diseases affecting the immune system and ranged from 14 to 89 years of age. The results of this study are summarized in Table I. The absolute number of peripheral blood lymphocytes (PBL) decreased with aging. The mean count was 2043 in the adult group (less than 60 years of age) and 1659 in the aged group (over 60 years of age). When T lymphocytes were assayed by rosette formation with neuraminidase-treated sheep erythrocytes in the presence of fetal calf serum after 1 hr incubation at 4°C, there was no difference in the proportions of T lymphocytes between the groups, whereas the proportions of T cells as assayed by rosette formation with sheep erythrocytes in the absence of fetal calf serum were significantly depressed in the aged group (p < 0.01). On the other hand, the proportion of T lymphocytes assayed by rosette formation with sheep erythrocytes after centrifugation at 1500 RPM for 5 min at room temperature was higher in the aged group than in the adult group (p < 0.02). The proportion of IgG-Fc receptor-bearing T lymphocytes detected by double rosette formation with sheep erythrocytes and chicken erythrocytes sensitized with rabbit IgG antibody was also higher in the aged than in the adult group (p < 0.05). The proportion of complement receptor-bearing lymphocytes did not change with aging. In addition, the proportion of surface Ig-bearing lymphocytes examined after being treated in pH 4.0 acetate buffer for 1 min to remove nonspecifically bound Ig from the cell surface showed no differences between the two groups. Response to PHA and concanavalin A was impaired in the aged (aged 70 to 83 years) compared to the young adult group (aged 20 to 40 years) (p < 0.01), whereas the response to pokeweed mitogen was of the same magnitude. PHA response was negatively correlated with the proportion of IgG-Fc receptor-bearing T cells. The mixed lymphocyte culture reaction with mitomycin-treated AL1 cells derived from Burkitt's lymphoma was also impaired in the aged group (p < 0.01) as was cell-mediated cytotoxicity to AL1 cells as target cells (p < 0.05). Levels of IgG and IgA in plasma were significantly higher in the aged than in the adult group (p < 0.001), whereas those of IgM and IgE were not different. Radioimmunoassay determination of Ig classes revealed that the geometric means of IgG, but not IgM or IgA, synthesized in vitro was significantly increased in the aged compared to the young adult group (p < 0.05) when PBL were cultured in the presence of PWM for 7 days. This increase in IgG synthesis in the aged group was attributed to enhanced T helper activity.

Suppressor Cells in Mice With Murine Mammary Tumor Virus-Induced Mammary Tumors. I. Inhibition of Mitogen-Induced Lymphocyte Stimulation 2 3

Suppressor cell activity was present in the glass-adherent fraction of spleen cells from C3H mice bearing murine mammary tumor virus-induced mammary tumors. These cells effectively suppressed the blastogenic response of syngeneic normal lymphocytes to concanavalin A (Con A). Suppression by the spleen cells from mammary tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing animals (TBA) by passage of the cells on glass wool columns increased the Con A response of the remaining cells by fourfold to eightfold. Characterization of the suppressor population indicated that the cells were also adherent to nylon wool but not to plastic and contained a significantly increased proportion of surface immunoglobulin-bearing and complement receptor-bearing lymphocytes. Depletion of macrophages and T-cells did not remove the suppressive activity from the spleens of the TBA. The results were consistent with the identification of the suppressor cell as a B-cell.

Antibody-dependent Lymphocyte-mediated Granulocyte Cytotoxicity in Man

Sera from two patients with granulocytopenia associated with collagen vascular disease caused the destruction of normal human granulocytes by autologous lymphocytes in vitro. Granulocyte cytotoxicity was measured by the release of 51Cr during incubation with test sera and lymphocytes in microtiter plates. Between 8% and 46% granulocytoxicity was produced in granulocytes from 8 normal donors by the sera from these two patients. Less than 6% granulocytotoxicity was seen with the sera from 14 normal subjects and 29 patient controls. Treatment of lymphocyte preparations with carbonyl iron and magnetic separation to remove phagocytic cells or treatment with complement-coated red cells followed by repeated gradient centrifugation to remove complement receptor-bearing lymphocytes did not reduce the granulocytotoxicity. There was a dose-response relationship between the concentration of positive sera and granulocytotoxicity. When these sera were fractionated by Sephadex G-200 gel filtration and by ion-exchange chromatography with DEAE-cellulose, the active component appeared in the IgG-containing fractions. Thus, IgG antibody-dependent, lymphocyte-mediated granulocyte cytotoxicity represents a means of detecting human granulocyte antibodies and is a possible mechanism of autoimmune neutropenia in these two patients.

Characterization of Cytolytic Effector Cells in Peripheral Blood of Healthy Individuals and Cancer Patients

Abstract Peripheral blood lymphocytes from patients with transitional cell carcinoma of the urinary bladder, from control tumor patients, and from healthy individuals were fractionated on columns retaining 1) cells with Fc-receptors for IgG, as defined by rosette formation with IgG-coated erythrocytes, 2) cells with surface-bound immunoglobulin, or 3) cells with both types of surface markers. The spontaneous cytotoxicity of these lymphocytes against allogeneic or autochthonous tumor cells of bladder carcinoma or unrelated origin was studied in a 51Cr-release assay. The cytotoxicity to allogeneic target cells of lymphocyte fractions depleted of B cells (SIg+ cells) was only slightly reduced, unchanged, or, occasionally, augmented when compared to that of unfractionated lymphocytes. Fractions containing the majority of the B cells present initially but depleted of most of the Fc-receptor-bearing lymphocytes (EA+ cells) displayed a strongly reduced cytotoxicity against the same tumor cells. These effector cell fractions were also depleted of a majority of the complement receptor-bearing lymphocytes (EAC+ cells) and of a minor but significant fraction of T cells (E+ cells) and of a minor but significant fraction of T cells (E+ cells). Removal of both SIg+- and Fc-receptor-bearing cells gave the same results. Thus, in most instances, the spontaneous cytotoxicity against allogeneic tumor cells of fractionated lymphocytes was similar to their K cell activity against chicken erythrocytes (Ec) in the presence of rabbit anti-Ec antibodies (preceding paper). In conjunction with other data on the immunoglobulin dependence of this spontaneous cytotoxicity these results suggest that a significant fraction of this reactivity, displayed by both tumor patients' and normal individuals' lymphocytes, may be antibody dependent. The antibodies may either be carried over cytophilically during lymphocyte isolation or may be formed and released by some antibody-producing cells during the in vitro incubation. In two cases, in which bladder cancer patients' lymphocytes were tested with both autochthonous and allogeneic target cells, the effector cells killing the autochthonous target cells were neither B cells nor Fc-receptor-bearing cells. These results suggest that different effector mechanisms were involved in these cases.

Antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC), definition of the "K cell" in the rat.

The nature and membrane characteristics of the "K cell" of antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC) were investigated in a widely used rat model of transplantation. Treatment of sensitized effector cell populations with anti-immunoglobulin and complement eliminated K cell cytotoxicity without diminishing the component of T cell-mediated injury. EA and EAC depletion experiments, although demonstrating no loss of K cell cytotoxicity after removal of complement receptor-bearing lymphocytes, produced a marked abrogation of cytotoxicity following the removal of the Fc receptor-bearing lymphocyte pool. Studies on phagocytic properties showed K cell activity to be shared by an adherent as well as a nonadherent cell population. Thus, the Fc receptor emerged as the only constant surface marker of the rat K cell in Ab-LMC.

T and CR+ lymphocyte profile in leprosy and the effect of treatment.

Thymus-derived lymphocytes (T lymphocytes) and complement receptor-bearing lymphocytes (CR+ lymphocytes) were estimated by using erythrocyte rosettes and erythrocyte-antibody-complement rosettes as markers in untreated lepromatous and untreated tuberculoid patients and in healthy controls. Treated lepromatous cases were also investigated. Ten cases of untreated lepromatous patients were reassessed 6 months or more after therapy commenced. A significant decrease in both percentages and absolute numbers of CR+ cells in the untreated lepromatous leprosy subjects was observed. This decrease showed a return to normal levels after treatment. The percentage of T cells in the untreated lepromatous cases was normal; however, the absolute numbers of T cells and the total lymphocyte count showed a significant decrease. After therapy, the T cell population was unchanged but the total number of lymphocytes increased significantly with treatment. The absolute number of T and CR+ cells was significantly less in the untreated than in the treated lepromatous patients.