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Biomedical subjects

T M Chused

Publications and source records attributed to T M Chused.

At least 73 records · Page 4Linked to original sources
PubMed1982

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Correlation with clinical features.

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.

Adult↗
PubMed1982

Biotinylation of human C3.

Purified human C3 was biotinylated using the biotinyl-N-hydroxysuccinimide imidoester (BNHS). Depending on the input of BNHS, from three to six molecules of biotin were incorporated per C3 molecule. The biotinyl-C3 retained over 90% of its specific hemolytic activity and when bound to sheep erythrocytes maintained its ability to adhere to human C3b receptors. These functions could be blocked by avidin. The biotinyl-C3 was fragmented normally to C3c and C3d in human serum and adsorption with avidin-Sepharose indicated that biotin moities were present in both fragments. Fluorescein-conjugated avidin reacted well with cell-bound biotinyl-C3b and was useful for quantitating C3 fixation by flow cytometry. Ferritin-conjugated avidin was used as a marker to characterize the distribution of biotinyl-C3b on erythrocytes by electron microscopy. These results suggest that biotinyl-C3 and avidin derivatives may be very useful tools for studies of many of the biological functions of C3.

Avidin↗
PubMed1982

Human lymphocytes with either the OKT4 or OKT8 phenotype produce interleukin 2 in culture.

In this study, we demonstrate that both highly purified T4+ and T8+ lymphocytes can produce substantial amounts of Interleukin 2(IL 2) when stimulated with the combination of concanavalin A (Con A) and phorbol myristate acetate. Furthermore, addition of IL 1 to macrophage-depleted T lymphocytes significantly increased IL 2 production by lymphocytes of either the T4+ or T8+ phenotype. These findings provide a basis for further studies of the molecular mechanisms involved in human immune cell interactions.

Cell Division↗
PubMed1982

Expression of Lyt-1 by a subset of B lymphocytes.

Using two-color flow cytometry and multiparameter data analysis, we have shown that the IgM bright, large subset of mouse splenic B lymphocytes express Lyt-1. This is not due to B cell uptake of immune complexes of Lyt-1 and antibody from T cells. The IgM bright cells of autoimmune NZB mice express more Lyt-1 than normal controls. This is because IgM containing plasmablasts, which are greatly increased in NZB spleens, are Lyt-1+. NZB spleen also contains more cells that are Lyt-1+ (but perhaps Lyt-1.2-), Thy-1.2 dull, and smaller in size than cells in normal mice. Thus, Lyt-1 is common to the T and B cell precursor or is induced independently during the ontogeny of T and at least one subset of B cells. We suggest that it be called Lyt-1.

Animals↗
PubMed1982

The human autologous mixed lymphocyte reaction. III. Immune circuits.

The human autologous mixed lymphocyte reaction represents the proliferative response of T cells to determinants presented on autologous non-T cells. Purified T4+ cells vigorously proliferate in response to stimulation by either (B + null) cells or M phi, whereas purified T8+ cells proliferate very little without a source of help. Such help can be provided by mitomycin C-treated T4+ cells, which indicates that proliferation of T4+ cells is not necessary for the help. M phi suppress the human AMLR, as measured by the response of T cells to stimulation by (B + null) cells. The target of this M phi-induced suppression was found to be the T4+ inducer cell. In contrast to the suppressive effects of M phi on T4+ cells, M phi did not suppress T8+ cells. The available data suggest that the human AMLR is a two-part inducer circuit. One part can be stimulated preferentially by M phi and the other by (B + null) cells; however, M phi prevent activation of the (B + null) cell part of the circuit. These results may provide an explanation for the differential activities of different regulatory circuits without and also with antigenic stimulation.

B-Lymphocytes↗
PubMed1982

Expression on normal lymphocytes of two cell surface antigens, XenCSA and GIX, related to the major glycoproteins (gp70) of murine leukemia viruses.

XenCSA and GIX are two cell surface antigens related to the major envelope glycoproteins (gp70) of murine leukemia viruses. The levels of expression of these gp70 determinants were assessed in 36 recombinant inbred mouse strains and selected backcrosses derived from crosses between C57BL/6 with DBA/2 and C3H/He. These two antigens segregated in backcross mice and showed a different strain distribution pattern among the recombinant inbred mice, demonstrating that XenCSA and GIX are distinct genetic markers for different endogenous gp70 sequences. It was also shown that independent sets of gene regulate the expression of XenCSA and GIX.

Animals↗
PubMed1981

Genetic control of B- and T-lymphocyte abnormalities of NZB mice in crosses with B10.D2 mice.

Parenteral NZB and B10.D2, F1 and F1 x B10.D2 mice were studied to determine the genetic control of (1) altered B-cell IgD expression, (2) plasma cell frequency, (3) IgM secretion per plasma cell, (4) primary in vitro cytotoxic T-cell responses to H-2-compatible cells, (5) production of thymocyte-binding antibodies, and (6) production of red-cell-specific antibodies. The results demonstrate that, in this cross, IgD abnormalities and production of red-cell-specific antibodies were recessive traits. There was a common genetic influence on plasma cell frequency, IgM secretion per plasma cell and production of thymocyte-binding antibodies which was distinct from the genes governing the ability to generate a cytotoxic T lymphocyte response to H-2-compatible cells.

Animals↗
PubMed1981

Wild mouse ecotropic murine leukemia virus infection of inbred mice: dual-tropic virus expression precedes the onset of paralysis and lymphoma.

NFS/N mice inoculated at birth with an ecotropic murine leukemia virus (Cas-Br-MuLV) obtained from wild mice developed hind limb paralysis beginning at 7 weeks of age and nonthymic lymphomas beginning at more than 20 weeks of age. Studies of 1- to 7-week-old Cas-Br-M MuLV-infected mice showed the following: (i) a marked increase in nonecotropic MuLV-related antigens on spleen cells but not thymocytes beginning at 2 weeks; (ii) the appearance of dual-tropic mink cell focus-forming (MCF) MuLV-related gp70 in spleen but not thymus or brain cells at 4 weeks; and (iii) the isolation of infectious MCF MuLV from spleen cells of 7-week-old mice. A role for MCF MuLV in Cas-Br-M MuLV-induced nonthymic lymphomas is indicated by these studies, and a role for recombinant MuLV in neurological disease is considered.

Animals↗
PubMed1981

Human neutrophil heterogeneity identified using flow microfluorometry to monitor membrane potential.

Previous studies of neutrophil nitroblue tetrazolium dye reduction in response to endotoxin and rosetting of IgG-coated erythryocytes have suggested functional heterogeneity of peripheral blood neutrophils. In the following study we utilized flow microfluorometry and the membrane potential-sensitive fluorescent dye 3-3'-dipentyloxacarbocyanine to assess the heterogeneity of neutrophils upon activation by a variety of stimuli. Unstimulated neutrophils from normal subjects exhibited a unimodal distribution of fluorescence, suggesting that all the cells possessed the same resting membrane potential. As neutrophils aged (>5 h), some cells lost fluorescence producing a bimodal distribution. In studies with fresh cells, the secretagogue phorbol myristate acetate (20 ng/ml) stimulated a uniform loss of fluorescence (apparent depolarization). The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) (0.1 muM) caused the neutrophils to assume and maintain (for > 30 min) a bimodal fluorescence distribution in which 65+/-5% of the neutrophils first decreased and then increased fluorescence (apparent depolarization/partial repolarization), and 35+/-5% of the cells exhibited either an increase in fluorescence (apparent hyperpolarization) or no change. Treatment of neutrophils with cytochalasin B before stimulation caused the cells to respond homogeneously to f-Met-Leu-Phe. Additional studies using neutrophils from patients with chronic granulomatous disease, which exhibit abnormal membrane potential responses, indicated that this defect affected all such neutrophils uniformly. These observations demonstrate the need to investigate the physiological significance of the heterogeneity of neutrophil function and indicate that the f-Met-Leu-Phe-induced changes in membrane potential observed in bulk population cell studies are the summation of two different responses.

Calcium↗
PubMed1981

Responder cells in the human autologous mixed lymphocyte reaction.

Isolated human T4+ cells proliferate in the autologous mixed lymphocyte reaction (AMLR), whereas isolated T8+ cells do not. However, in the presence of Interleukin 2 or T4+ cells, the T8+ cells demonstrated substantial proliferation. These studies suggest that T8+ cells recognize signals from autologous non-T cells, but require an additional factor for the subsequent proliferative response. Since this stimulus can be provided by T4+ cells, the AMLR appears to constitute an inducer circuit. Different defects in this circuit may be responsible for the common abnormality of the AMLR in different diseases.

Antibodies, Monoclonal↗
PubMed1981

Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry.

Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence-activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis.

Cell Adhesion↗
PubMed1980

Sjögren's syndrome (Sicca syndrome): current issues.

This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjögren's syndrome alone (primary) and Sjögren's syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjögren's syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.

Antigen-Antibody Complex↗
PubMed1979

CBA/N X-linked B-cell defect prevents NZB B-cell hyperactivity in F1 mice.

NZB mice and their F1 hybrids produce excessive polyclonal IgM and autoantibodies of both IgM and IgG classes. CBA/N mice and CBA/N-mothered F1 males fail to make antibody to many T-independent antigens and have low levels of serum IgM; further, these mice lack a population of splenic B cells characterized by a low-to-intermediate density of surface IgM. We have studied male CBA/N, NZB, CBA/N X NZB, NZB X CBA/N, and CBA/J mice; female CBA/N X NZB mice; and males of several control crosses of NZB and CBA/N mice. We have found that the CBA/N X-linked defect of T-independent immune response is completely expressed in CBA/N X NZB mice. In marked contrast to NZB mice and to NZB mice and to NZB F1 hybrids bearing at least one normal X chromosome, the CBA/N X NZB males failed to respond to two T-independent antigens, had small numbers of splenic IgM-producing cells, barely detectable splenic IgM production, and splenic B-cell surface-Ig patterns resembling those of CBA/N mice. These data suggest that the NZB B-cell abnormality resulting in excessive IgM production occurs almost exclusively in that population of B cells affected by the CBA/N X chromome-linked defect. Preliminary studies suggest that CBA/N X chromosome retards the spontaneous development of anti-erythrocyte autoantibodies in CBA/N X NZB males. Castration, known to accelerate autoimmune disease in certain NZB F1 males, appears to have no influence on the immune functions examined in this study.

Animals↗