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Biomedical subjects

M C Mingari

Publications and source records attributed to M C Mingari.

At least 109 records · Page 6Linked to original sources
PubMed1982

Role of Ia antigens in the human autologous mixed lymphocyte reaction.

The role of Ia antigens in the human autologous mixed lymphocyte reaction (MLR) was analyzed. To do this, different mononuclear cell populations were fractionated according to their Ia antigen expression and used as stimulating cells in autologous MLR. Also examined was the effect of two hybridoma monoclonal antibodies specific for human Ia molecules on the autologous MLR. The results show that the stimulating capacity of peripheral blood mononuclear cells is restricted to Ia-bearing cells. While peripheral blood T cells are unable to function as stimulating cells, highly purified Ia+ mixed lymphocyte culture-activated T cells are very effective. The possibility that Ia molecules are directly involved in the autologous MLR is further substantiated by the strong inhibitory effect of monoclonal anti-Ia antibodies.

Antibodies, Monoclonal↗
PubMed1982

Surface markers of cloned human T cells with helper or suppressor activity on pokeweed mitogen-driven B cell differentiation.

Human spleen T cells stimulated with pokeweed mitogen (PWM) were cloned under limiting conditions in microculture systems using interleukin 2 and irradiated autologous cells. Clones were screened for helper or suppressor activity on PWM-dependent B cell differentiation by adding cell aliquots to either isolated B cells and PWM or to mixtures of T and B cells and PWM. Out of 97 clones tested, 14 promoted intense B cell differentiation, as assessed by measurements of secreted IgG, and 6 strongly inhibited B cell maturation induced by spleen T cells. All the selected clones maintained their original activity after short-term clonal expansion; in addition, a similar (helper or suppressor) effect was detected when the total number of plasma cells per well was evaluated. Suppressor clones had no cytolytic activity on autologous T and B cell blasts, K562 cells or antibody-coated L 1210 mouse cells. Nine helper and 6 suppressor clones were analyzed for a battery of surface markers. All the clones were E rosette-positive and expressed HLA-DR (Ia) antigens. Fcmu receptor was present on a single helper clone, whereas Fc gamma receptor was expressed on a suppressor clone only. All but two clones expressed the OKT4+/ OKT8-, a single suppressor clone was OKT8+/OKT4-, whereas coexpression of OKT4 and OKT8 antigens was detected in one helper clone. Thus, the claim that helper T cells are OKT4+/OKT8- and suppressor T cells are OKT4-/OKT8+ is not supported by the analysis of their phenotype at the clonal level.

Antibodies, Monoclonal↗
PubMed1982

Human T cell subpopulations defined by a monoclonal antibody. I. A small subset is responsible for proliferation to allogeneic cells or to soluble antigens and for helper activity for B cell differentiation.

A monoclonal antibody (5/9) was obtained that reacts with the majority of alloactivated human T cells but only with 15 to 20% peripheral T cells. The populations reactive with the 5/9 antibody were separated from the remaining T cells by rosetting techniques using 5/9-coated ORBC. 5/9+ and 5/9- populations were analyzed for different in vitro activities. The helper activity of PWM- driven B cell differentiation appeared to be restricted and highly enriched in the 5/9+ population. In addition, 5/9+ cells contained all the cells capable of proliferation to tetanus toxoid and allogeneic cells. Thus, in vitro activities commonly used for evaluation of T cell function seem to be confined to a small fraction of peripheral T cells.

Animals↗
PubMed1982

Human T cell subpopulations defined by a monoclonal antibody. II. Evidence for cell cooperation in the response to alloantigens and generation of cytolytic cells.

It has been shown previously that the 5/9 monoclonal antibody defines a small T cell subpopulation in human peripheral blood that includes all the cells responsible for proliferation to tetanus toxoid and to alloantigens as well as the helper cells for B cell differentiation. In the present study, human peripheral blood T cells were fractionated according to their reactivity with the 5/9 monoclonal antibody and stimulated in mixed lymphocyte culture (MLC). In spite of a strong proliferative response in MLC, 5/9+ cells generated no cytolytic activity against PHA-activated lymphocytes bearing the stimulating alloantigens (CTL activity) or against the K562 human cell line (NK activity). The precursors of these cytolytic effector cells were present in the 5/9- fraction. However, 5/9+ cells or soluble factors derived from 5/9+ cells were needed to induce 5/9- cells to respond in MLC and develop cytolytic activity. Both 5/9+ and 5/9- cell populations, upon MLC stimulation, were able to lyse L1210 mouse lymphoma cells in the presence of specific antibodies (ADCC).

Animals↗
PubMed1981

Surface markers of cloned human T cells with various cytolytic activities.

Human T cells stimulated in secondary allogeneic mixed lymphocyte culture (MLC) were cloned under limiting conditions in microculture systems using T cell growth factor and irradiated allogeneic cells. Clones with lytic activity against either phytohemagglutinin-induced blast cells bearing the stimulating alloantigen(s) (cytotoxic T lymphocyte [CTL] activity), L1210 mouse lymphoma cells coated with rabbit antibody (antibody-dependent cell-mediated cytotoxicity [ADCC]), or K562 human target cells were selected, expanded, and then analyzed for different surface markers, including rosette formation with sheep erythrocytes (E rosettes), receptors for the fc portion of IgG or IgM (Fc gamma R and Fc mu R), and a group of antigens recognized by monoclonal antibodies including Ia, 4F2, OKT8,a nd OKT4. All the cytotoxic cells were E rosette+, Ia+ and 4f2+. Expression of Fc gamma R was restricted to the clones active in ADCC. CTL clones were either OKT8+ or OKT8-. Furthermore, three of the OKT8- CTL clones were OKT4+. In addition, some cytolytic clones devoid of specific CTL activity were OKT8+. It thus appears that the claim that human CTL are OKT8+, OKT4-, and Ia- is not supported by the analysis of their phenotype at the clonal level.

Antibodies↗
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

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

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↗
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↗