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Biomedical subjects

L Moretta

Publications and source records attributed to L Moretta.

At least 289 records · Page 16Linked to original sources

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↗

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↗

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↗

Imbalances in T cell subpopulations in multiple sclerosis patients.

Abnormal proportions of a distinct T cell subpopulation able to bind IgG immune complexes (T.G cells) were found in peripheral blood samples from patients with MS. About 50% of the patients examined had an overabundance of T.G cells. The possible role of these cells in the pathogenesis of MS is considered.

Blood Cell Count↗

Fc-receptor heterogeneity of human suppressor T cells.

Concanavalin A (Con A) stimulated the IgM-binding subpopulation of human T cells (TM) to suppress the pokeweed mitogen-induced differentiation of B lymphocytes to plasma cells. Control TM cells that had not been Con A activated did not suppress. The degree of suppression was related to the number of Con A-TM cells added to the cultures and it was abolished by irradiation of the T lymphocytes either before or after the 24-hr culture period with Con A. Suppression did not require the presence of TG cells, whose suppressor potential has been previously established. These findings indicate that suppressor activity is not confined to the TG subpopulation but may be expressed by TM cells also.

B-Lymphocytes↗

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↗

Spontaneous cell-mediated cytotoxicity in humans. Distribution and characterization of the effector cell.

When lymphocytes from healthy donors were tested as effector cells, the cytotoxic activities observed in spontaneous and in antibody-dependent cell-mediated cytotoxicity were positively correlated. However, with lymphocyte preparations obtained from renal patients, a dissociation between the two activities was occasionally observed. Human natural killer cells are lymphocytes, with receptors for the Fc fragment of IgG molecules, but with no surface immunoglobulin. Their cytotoxicity is reduced by the presence of granulocytes or monocytes. After separation of rosetting and non-rosetting cells with AET- (2-aminoethylisothiouronium bromide hydrobromide) or neuraminidase-treated sheep erythrocytes, the majority of the activity was recovered in the non-rosetting fraction, but a portion of it was present consistently in the rosetting cell fraction. Cells in the latter fraction also displayed receptors for the Fc fragment of immunoglobulin G.

Adult↗

Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG.

Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.

Antibody-Producing Cells↗

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↗

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↗

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↗

Receptors for IgG molecules on human lymphocytes forming spontaneous rosettes with sheep red cells.

A mixed rosette technique with sheep red blood cells (SRBC) and ox erythrocytes heavily coated with rabbit antibody (EA) was employed to simultaneously identify human peripheral blood T lymphocytes and IgG receptor-bearing cells. The findings of a noticeable proportion of "mixed rosettes" in peripheral blood lymphocytes freshly drawn from normal individuals and of an even higher number of these mixed rosettes in cell suspension kept in culture media supplemented with fetal calf serum provide evidence for the capacity of human T cells to express membrane receptors for antigen-antibody complexes.

Binding Sites↗