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Biomedical subjects

L Moretta

Publications and source records attributed to L Moretta.

At least 271 records · Page 15Linked to original sources
PubMed1981

Phenotypic characterization of human cytolytic T lymphocytes in mixed lymphocyte culture.

Mixed lymphocyte reaction (MLR)-activated T cells were analyzed according to the expression of various cell surface markers by the specific cytotoxic T lymphocytes (CTL) generated in the MLR. CTL were found exclusively in a population of MLR-activated T cells that lacked detectable Fc gamma R but that expressed a surface antigen recognized by the 4F2 monoclonal antibody. In contrast, CTL were found in both the Ia-positive and Ia-negative cells after MLR activation. Thus, the specific CTL generated in the allogeneic MLR can be identified and isolated by virtue of the expression of a particular cell surface marker.

Antigens, Surface↗
PubMed1981

Surface antigens specifically expressed by activated T cells in humans.

By immunizing BALB/c mice with human T cells derived from a secondary mixed lymphocyte reaction (MLR) and successive fusion of the spleen cells with P3X63Ag8U1 myeloma cells, several monoclonal antibodies to activated T cells were obtained. Four of them (MLR 1-4) were shown to be specific for activated T cells only, showing no reactivity with peripheral blood cells. The antigens recognized by these antibodies are differently distributed and appear on T cells at different times after stimulation. Thus, MLR2 stains nearly all the responder T cells present in a secondary MLR, while MLR 1, 3 and 4 stain only a fraction. MLR2 and 3 are also present on mitogen-stimulated cells. At least 3 of these MLR antigens may define different sets of activated T cells, and are likely to become useful in monitoring T cell activation also in the course of diseases involving the immune system.

Animals↗
PubMed1981

Human T lymphocytes subpopulation as defined by alloantigens and FC receptors a comparative analysis.

Human peripheral T cells were fractionated in accordance to their surface receptors for G or M immunoglobulins and analyzed for their reactivity with alloantisera obtained by planned immunization involving HLA-A and HLA-B compatible individuals. These alloantisera were previously shown to recognized polymorphic structure exclusively expressed on T cells. Although the majority of the alloantisera analyzed reacted with different proportions of both T(M) and T(G) populations, some antisera specifically recognized surface structure restricted to either T(M) or T(G) lymphocytes. The various alloantisera consistently reacted with a fraction only of T(G) and T(M) cells, this indicating that these T cell subsets can be further fractionated in accordance to the expression of the alloantigenic determinants recognized by these antisera.

Animals↗
PubMed1981

Fc receptors on human T lymphocytes: loss of Fc mu and expression of Fc gamma receptors by T cells stimulated in mixed lymphocyte reaction.

The consequences of allogeneic stimulation on the expression of Fc mu or Fc gamma receptors were analysed in T-cell populations responding in mixed lymphocyte reaction (MLR). Unfractionated T-cell populations were cultured with a pool or irradiated allogeneic T-depleted cells. The responder E-rosetting cells progressively lost Fc mu and acquired Fc gamma receptors. The change of the original Fc receptor phenotype is not the consequence of a preferential proliferative response of TG versus TM cells but is likely due to a de novo expression of Fc gamma receptors by T cells lacking detectable Fc receptors (T-null) and also to the loss of Fc mu and expression of Fc gamma receptors by TM cells. These data suggest that, after MLR, responder T cells can modify their Fc receptor phenotype.

Animals↗
PubMed1981

Regulation of IgG antibody-dependent cellular cytotoxicity in vitro by IgM antibodies.

IgM antibodies have previously been reported to either inhibit or induce antibody-dependent lymphocyte cytotoxicity (ADCC). Here we show that human lymphocytes lyse bovine erythrocytes (Eb) in the presence of either IgM of IgG anti-Eb from rabbits. Seven out of 20 IgM preparations (Sephadex G-200) were ADCC-active. IgG-dependent ADCC was inhibited by human IgG but not by IgM. In contrast, IgM ADCC was inhibited by both IgG and IgM. The effector cells in IgM ADCC were a subpopulation of lymphocytes with distinct Fc receptors for both IgG and IgM. Most of them also had sheep erythrocyte receptors. Extensive purification of the ADCC-active IgM antibody preparations indicated that very small amounts of contaminating IgG anti-Eb were responsible for ADCC induction. When purified and ADCC-inactive IgM antibodies were mixed with suboptimal concentrations of IgG antibodies, a strong enhancement of ADCC was found. To achieve enhancement, the two antibody isotypes had to be present on the surface of the same target cells, and the IgM effect was not due to the release of soluble ADCC-enhancing factors. Thus, in this system, IgM antibodies are not capable of inducing ADCC on their own. However, they enhance ADCC by improving the contactual interaction between target cells and a special subset of effector cells.

Animals↗
PubMed1981

Human T-lymphocyte subpopulations in Hashimoto's disease.

An inherited defect os suppressor T-lymphocytes has been hypothesized in Hashimoto's thyroiditis. To assess this hypothesis, human T-lymphocyte subsets (TG, T lymphocytes with surface receptors for the Fc fragment of immunoglobulin G; TM, T lymphocytes with Fc receptor for immunoglobulin M) have been studied in nine patients affected by the disease. To cells have been previously shown to be suppressors in the pokeweed mitogen-stimulated B-cell differentiation and have proved abnormal in several autoimmune or immunodeficiency disorders. The number of TG lymphocytes in the patients did not differ from that in normal controls. It is possible that 1) suppressor T-lymphocytes are not involved in the pathogenesis of Hashimoto's disease or 2) antigen-specific suppressor T-cells are involved, but too are low in number with respect to total TG.

Adult↗
PubMed1981

Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure.

T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

Bone Marrow Cells↗
PubMed1981

Distribution and properties of Fc receptors for IgG on different leucocyte populations in man.

The distribution and some characteristics of Fc receptors for immunoglobulin (Fc gamma R) were analysed on different human leucocyte populations. Interaction of Fc gamma R present on T gamma cells with ox erythrocytes-IgG immune complexes (IgG-IC) provides a switch-off signal for the expression of the Fc gamma R themselves; in addition, these receptors are sensitive to the proteolytic activity of pronase. Since both of these phenomena could have important effects on certain functional activities of the cells, we have analysed the effect of the interaction between IgG-OxE and the Fc gamma R present on various leucocyte populations. The large majority of T gamma cells or of tonsil B cells lost their Rc gamma R after interaction with IC; IC, in turn, had no effect on the Fc gamma R of AC and PMN. Twelve to 22% of the non-T, non-AC fractions retained surface Fc gamma R. Enzymatic treatment of the cells showed that T cells, non-T, non-AC and B cells have Fc gamma R sensitive to pronase, whereas Fc gamma R present on AC and PMN are resistant even to very high concentrations of the enzyme.

Antigen-Antibody Complex↗
PubMed1980

Human T lymphocyte subpopulations defined by Fc receptors and monoclonal antibodies. A comparison.

Human T cell subpopulations have been defined on the basis of differential expression of either Fc receptors or specific cell-surface antigens. In this study, we utilized a series of monoclonal antibodies reactive with T cells, monocytes, and Ia antigens to characterize isolated subpopulations of T cells bearing receptors for the Fc portion of IgG (T gamma) and subpopulations of T cells bearing receptors for the Fc portion of IgM T mu. The results showed that the T mu population contained both inducer (OKT4+) and cytotoxic/suppressor (OKT5+) populations and was similar to the unfractionated T cell population, whereas the T gamma subset contained few T lymphocytes (OKT3+) and was not enriched for either T cell subset defined by these monoclonal antibodies. Rather, the T gamma population was comprised largely of Ia- cells possessing a monocyte antigen (OKM1+). In reciprocal studies, it was found that both isolated OKT4+ and OKT5+ T cell subsets contained few T gamma cells, whereas both subsets were mainly comprised of T mu cells. We conclude that there is little correlation between T cell subsets defined by these monoclonal antibodies and those defined by Fc receptors.

Antibody Specificity↗
PubMed1980

T cell subpopulations after allogeneic bone marrow transplantation.

T-cell subpopulations were studied in six patients after allogeneic bone marrow transplantation for aplastic anemia and acute leukaemia, by means of receptors for IgG (TG-cells) and IgM (TM-cells). Significant modifications of TM-TG levels were found: a 2 to 10 fold increase of TG cells and a 2 to 10 fold decrease of TM cells from pre-transplant levels could be observed. The TM-TG imbalance appeared together with the clinical signs of GVHD: the level of TM-depression (but not the level of TG increase) correlated with the severity of GVHD. The TM-TG modifications were observed as long as 3 years after transplantation, also in the absence of signs of GVHD. In addition, all six patients were found to have severely impaired pokeweed-induced B-cell differentiation. The clinical implications and the possible lack of T-helper activity are discussed.

Acute Disease↗
PubMed1980

Suppressor activity of T cells bearing Fc receptors for IgG on lymphoid colony formation.

Human T lymphocytes, upon phytohaemagglutinin stimulation, are able to form colonies in semisolid media. Peripheral T cell bearing Fc receptors (TG) were studied for their possible regulatory activity on lymphoid colony development. Although no substantial differences were observed between the cloning efficiency of unfractionated T cells (thus including TG cells) and T cells depleted of TG, a sharp suppression of colony formation occurred when positively selected TG cells were readded to TG-depleted suspensions. Therefore, TG suppressor activity seems to be strictly dependent upon cell interaction with ox IgG immune complexes used for TG cell isolation. Different experimental approaches failed to demonstrate, although did not exclude, that suppression in this system is mediated by soluble factors. gamma-irradiation of TG cells abrogated their suppressor capacity.

Cells, Cultured↗
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

Natural cytotoxicity of human Fc gamma-receptor-positive T lymphocytes after surface modulation with immune complexes.

In humans T cells with surface receptors for the Fc fragment of IgG (Fc gamma receptors) (TG cells) are effector cells in antibody-dependent cellular cytotoxicity (ADCC) and in natural cytotoxicity. While Fc gamma receptors are required to mediate ADCC, their role in natural cytotoxicity is unknown. To investigate this question, Fc gamma receptors on effector cells were modulated by interaction with IgG immune complexes. As a consequence of this modulation, TG cells lost most of their ADCC activity but retained a significant part of their natural killer activity. Thus, these experiments demonstrate that the cytotoxic mechanisms exerted by the same cell population can be dissociated experimentally. Furthermore, they suggest that the net natural cytotoxicity of normal human lymphocytes in certain effector cell-target cell combinations is the result of distinct types of reaction.

Antibody-Dependent Cell Cytotoxicity↗