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Biomedical subjects

M C Mingari

Publications and source records attributed to M C Mingari.

At least 127 records · Page 7Linked to original sources
PubMed1980

Immune suppression of hematopoiesis in aplastic anemia: activity of T-gamma lymphocytes.

In vitro colony formation (CFU-c) was studied in 7 patients with severe aplastic anemia (SAA) in complete autologous hematologic reconstitution. Colony formation was depressed in all patients (less than 5% of normal). Further studies showed that 1) patients' colony formation could be enhanced by removing T cells from the marrow, but not by removing adherent cells (AC); 2) patients' marrow cells showed a marked CFU-c inhibition against normal allogeneic marrow; 3) CFU-c/suppression could be reduced by removing T cells from the patients' marrow before the co-culture experiments; 4) patients' marrow T cells showed significant CFU-c/inhibition against autologous as well as against allogeneic unrelated normal marrow cells; 5) irradiation with 1500 rads of T cells abrogated their suppressor activity; 6) the latter was found mainly in marrow T cells with IgG receptors (TG+ cells) as well as in the supernatant of marrow T cells cultured overnight; 7) TG+ cells derived from normal donors had no significant CFU-c/inhibitory activity against autologous or allogeneic marrow cells. Active myelosuppression would thus be detectable in patients with SAA in remission and would appear to be mediated by marrow T cells with IgG receptors.

Adolescent↗
PubMed1979

Human T-lymphocyte subpopulations: alterations in systemic lupus erythematosus.

Sharply reduced proportions of T cells with Fc receptors for IgG (TG cells) were observed in blood samples from patients with systemic lupus erythematosus (SLE), mainly with active disease. This T-cell subset has previously been shown to be a suppressor in the pokeweed mitogen (PWM)-dependent B-cell differentiation. In contrast, the percentages of T cells with Fc receptors for IgM (TM cells), which have been shown to help immunoglobulin production, were not different from those of normals. TG cells present in the circulation of SLE patients were analysed for their functional capacities in antibody-dependent cell-mediated cytotoxicity and in the suppression of a PWM-induced B-cell differentiation. In both these assays TG cells from SLE patients had normal effector cell activity. This suggests that thr than a qualitative type.

Adolescent↗
PubMed1979

Bone marrow transplantation for severe aplastic anemia. A report of 9 cases.

9 patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation (BMT). 5 were conditioned with cyclophosphamide and received and HLA-identical graft (4 patients) or a mismatched graft (1 patient): 1 rejected the graft on day 30 and died on day 34 during conditioning for a second transplant; 1 died on day 15 with acute and severe graft versus host disease (GvHD) in the absence of haemopoietic engraftment; 3 are alive and complete chimeras at 1,069, 490 and 332 days after transplantation. GvHD developed in 4 patients and was treated successfully in 3 with high dose methylprednisolone and/or antilymphocytic globulin (ALG). 4 patients were conditioned with ALG and received bone marrow from a haploidentical sibling or parent: 1 patient was refractory; 3 patients showed evidence of hematologic reconstitution, but 2 of these required a second course of ALG. 3 patients in this group are alive between 60 and 490 days; 1 patient died on day 121 of HBSAg-negative acute hepatitis.

Adolescent↗
PubMed1979

Immunoregulatory subpopulations of human T lymphocytes.

Human T lymphocyte subpopulations can be identified on the basis of surface receptors for G or M immunoglobulins (TM and TG cells respectively). Isolated TM or TG cells can be analyzed in vitro for their morphology and their functional properties. In addition to unique characteristics observed in light and electron microscopy, TM and TG cells show a different pattern of responsiveness to PHA and alloantigens. The major functional difference so far observed concerns their interaction with B lymphocytes. TM cells provide help for the T-dependent responses of B lymphocytes to pokeweek mitogen (PWM), whereas TG cells suppress B lympohcyte activation in this in vitro system by inhibiting helper TM cells. Imbalances and/or functional alterations of TM and TG cells are present in various immunological disorders and are possibly involved in the pathogenesis of these diseases.

Antibody Formation↗
PubMed1979

Imbalances of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy.

Reduced numbers of T cells with Fc receptors for IgG (TG cells) are present in blood samples of patients with respiratory allergic disease, mainly those with severe symptoms. TG cells have been previously shown to be suppressor in the pokeweed mitogen- (PWM) dependent B cell differentiation. T cells with Fc receptor for IgM (TM cells), which help immunoglobulin production, are in a normal range. After specific hyposensitization, resulting in a sharp improvement of clinical symptoms, TG cell subset reached normal values.

Adolescent↗
PubMed1978

Morphological and histochemical analyses of two human T-cell subpopulations bearing receptors for IgM or IgG.

Two subpopulation of circulating human T cells forming rosettes with neuraminidase-treated sheep erythrocytes were purified on the basis of the presence of receptors for IgG (TG cells) or for IgM (TM cells), and were shown to have distinguishing morphological and histochemical characteristics. TM cells had the general features of typical small- or medium-sized lymphocytes; most were easily identifiable by distinctive cytoplasmic accumulations, usually one and sometimes two large spots, of nonspecific acid esterase activity. The release of the vesicular contents on short-term culture of TG cells was inhibited by cytochalasin B. Definition of these distinguishing characteristics of TM and TG cells provides a basis for practical enumeration of these functionally distinct subpopulations of human T cells. Some of the TG cells were capable of endocytosis of IgG antibody-coated erythrocytes.

Binding Sites, Antibody↗
PubMed1978

Fc-receptors for IgG and IgM immunoglobulins on human T lymphocytes: mode of re-expression after proteolysis or interaction with immune complexes.

The susceptibility to proteolysis and the mode of re-expression of receptors for IgM or IgG present on two different subpopulations of human T lymphocytes (T.M and T.G cells, respectively) have been investigated. The IgM receptor was highly susceptible to both trypsin and pronase, whereas the IgG receptor was resistant to trypsin and sensitive only to high concentrations of pronase. The receptors have been removed by treating purified human T cells with pronase and their reappearance on the cell surface has been followed in vitro. The IgM receptors on the cell surface were detectable within 2 hr and the resynthesis was completed in 6 hr. IgG receptors were detectable in 4 to 6 hr and the resynthesis completed within 12 hr. When protein synthesis was inhibited by culturing the cells in the presence of cycloheximide for up to 12 hr, only the IgM receptor (which had a higher turnover rate) failed to be expressed. Whereas interaction of IgG immune complex with the IgG receptors was previously shown to induce a modulation of the receptors, contact with antigen-IgM antibody complexes did not alter the mode of expression of IgM receptors.

Antigen-Antibody Complex↗
PubMed1977

Imbalances in T cell subpopulations associated with immunodeficiency and autoimmune syndromes.

Abnormal proportions of the distinct T cell subpopulations binding the Fc portion of IgM (T-M) cells and those bearing receptors for the Fc portion of IgG (T-G) cells, were observed in blood samples from patients who had congenital or acquired abnormalities of the thymus, severe combined immunodeficiency, or an unexplained primary deficiency in cell-mediated immunity; most had too few circulating T-M cells and often an overabundance of T-G cells. In an in vitro evaluation of lymphocyte from one of three thymoma patients with an elevated T-G subpopulation, removal of T-G cells abrogated the suppression of T-M cell help of B cell differentiation induced by pokeweed mitogen. A spectrum of patients with sex-linked infantile agammaglobulinemia, variable hypogammaglobulinemia, and selective IgA deficiency, and a few patients with autoimmune syndromes infrequently had distorted representation of these T cell subpopulations in the circulation. This suggests that B cell dysfunction in many of these patients is not merely due to numerical excesses or insufficiencies of helper or suppressor T cells.

Autoimmune Diseases↗
PubMed1976

Human T cell receptor for IgM: specificity for the pentameric Fc fragment.

The specificity of the IgM receptor expressed by human T cells cultured in IgM-free media has been investigated. IgM receptors have been detected using a rosette system with ox erythrocytes coated with rabbit antibody (EA(IgM)), and the inhibitory capacity of different IgM fragments in the rosette system has been tested. It was found that F(c)5mu but not F(ab')2mu, nor monomeric IgM (8 S IgM) inhibited EA (IgM) rosette-forming cells. This indicates that the receptor present on the surface of T cells has affinity for a structure located in the Fc portion of the pentameric IgM.

Binding Sites↗
PubMed1976

Subpopulations of human T cells identified by receptors for immunoglobulins and mitogen responsiveness.

Human T lymphocytes in peripheral blood have been shown to have receptors for IgG (Tgamma) or IgM (Tmu). Cultured Tgamma cells do not express receptors for IgM and purified Tmu cells do not have receptors for IgG, thus they appear to be distinct T cell populations. Although the two subpopulations show similar response patterns to concanavalin A, Tmu and Tgamma cells exhibit different dose-response curves to phytohemagglutinin. The normal response pattern to phytohemagglutinin requires a mixture of T cell subpopulations suggesting that synergistic interactions may occur.

Binding Sites, Antibody↗
PubMed1975

Expression of a receptor for IgM by human T cells in vitro.

The capacity of human peripheral blood lymphocytes (PBL) to bind antigen-IgG antibody (EA(IgG)) and antigen-IgM antibody (EA(IgM)) complexes was investigated using a rosette technique with ox erythrocytes coated with rabbit IgG or IgM antibody. It was found that while EA(IgG)-rosette-forming cells (RFC) were detected on PBL freshly drawn from normal individuals, EA(IgM)-RFC were present only in suspensions kept in culture for 24 h in mediá supplemented with sera containing very low or no amounts of IgM. Experiments of simultaneous detection of EA(IgG)-RFC or EA(IgM)-RFC and other membrane markers for human T or B cells together with experiments on purified T or B cell populations indicated that EA(IgG)-RFC were formed by both T and B cells, while T cells only were capable of EA(IgM) rosette formation. The specificity of the receptors for IgG and IgM was determined by studying the inhibitory capacity of purified human IgM and IgG in the rosette assay. The receptor for IgG was inhibited by IgG and not by IgM, while the reverse was true for the receptor for IgM.

Antigen-Antibody Complex↗
PubMedDate not supplied

Partial inefficiency of T cell receptors gamma/delta composed of a heavy (55-kD) gamma chain to mediate cell activation upon binding to specific monoclonal antibodies.

We analyzed CD8+ T cell receptor (TCR) gamma/delta+ (delta-TCS-1 reactive) cell clones expressing the 55-kD gamma chain for their susceptibility to triggering by monoclonal antibodies (mAbs) specific for TCR or CD3 molecules. Clones were derived by limiting dilution from CD3+, WT31- FACS-purified peripheral blood populations or CD4-CD8- thymocytes (a fraction of the latter cells expressing de novo CD8 surface antigen upon culture in IL-2). Clones were screened according to their reactivity with both anti-CD8 and delta-TCS-1 mAbs. Analysis of CD3-associated molecules immunoprecipitated by anti-Leu-4 (anti-CD3) mAb under conditions which preserve the CD3/TCR association (1% digitonin) showed a predominant 55-60-kD molecule both under reducing and non-reducing conditions. All clones expressing the delta-TCS-1+ CD8+ surface phenotype derived from either thymus or peripheral blood lysed the Fc gamma receptor-bearing P815 target cells in the presence of anti-CD3 mAb. On the other hand, delta-TCS-1 mAb was poorly efficient in triggering the lytic machinery of these clones, while it induced target cell lysis by delta-TCS-1+ CD8- clones.

Animals↗
PubMedDate not supplied

Heterogeneity of B cell growth factor (BCGF)-producing T cells in humans. Clonal analysis of BCGF-producing cells within T4+ and T8+ subsets and evidence for the involvement of different growth factors in different BCGF assays.

Human peripheral blood T cells were cloned under conditions allowing the clonal expansion of virtually all T cells. Clones derived from T4+ or T4- (T8+) subsets were screened for their ability to induce B cell proliferation either in the Staphylococcus aureus Cowan-I (SAC)-driven assay or in the costimulation assay based on the use of anti-mu antibodies. BCGF activity in the SAC- and in the anti-mu-driven system was displayed by 13% and 15% T8+ clones, respectively, while 74% and 79% T4+ clones had BCGF activity in the same assay. SN of clones with BCGF activity were further screened for their susceptibility to the inhibition by CM 269 (anti-IL-2 receptor) monoclonal antibody. All clones were inhibited in the SAC assay, whereas several clones were partially or totally resistant to inhibition in the anti-mu assay. Nine of such non-inhibited clones were further analyzed for their ability to produce gamma-IFN (known to act as a BCGF) and IL-2: six of them were found to produce gamma-IFN, while none produced any detectable IL-2 activity.

Cells, Cultured↗
PubMedDate not supplied

Both the precursors and the effectors of human lymphokine-activated killer (LAK) cells may belong to T lymphocytes.

The present experiments were designed to perform a further investigation of the cell lineage of lymphokine-activated killer (LAK) cells. In the presence of adherent cells both T and not-T cells, separated on the basis of rosette formation with sheep erythrocytes (E rosettes), generated LAK activity after short-term culture in recombinant interleukin-2 in 5 different individuals tested. Since at the termination of the culture more than 98% of cells were T11-positive, it is evident that both LAK precursor and effector cells may belong to the T cell lineage. By applying a culture technique which allows the clonal expansion of virtually all T cells, we further selected and analyzed T cell clones with LAK activity. Under the culture conditions used, LAK clones represented approximately 4% of all proliferating clones. All had cytolytic activity against K562 target cells as well and also released large amounts of gamma-interferon following phytohemagglutinin stimulation.

Antigens, Surface↗