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Biomedical subjects

L Moretta

Publications and source records attributed to L Moretta.

At least 307 records · Page 17Linked to original sources
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

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↗
PubMedDate not supplied

Surface markers of human T lymphocytes.

Surface markers have been extensively used for the identification and fractionation of different sets of human lymphocytes. Although they have proven useful for the identification of different cell subpopulations and for delineating various stages of T cell maturation or activation, there are a number of limitations in their application that should be carefully considered. In most instances, markers which are reported as defining functional subpopulations are not directly involved in the functional capability to be defined. In addition, a precise correlation between surface markers and cell function is difficult if only a small percentage of the cells in a given subset is involved in the functional activity measured. It is also clear that cell activation and differentiation, or mechanisms of cell fractionation, may affect the expression of some surface markers. Moreover, the assumption that functional activities ascribed to cell subsets or to surface markers in vitro are also operating in vivo may be incorrect. Human T cell surface markers can be grouped in various (as well as overlapping) categories, namely those recognizing the total T cell population, those present on T cell subsets and those expressed only on T cells at a given stage of maturation or as a consequence of cell activation. A more precise correlation between the presence of surface markers and the expression of functional activities can be performed by more complex experimental approaches such as the combined use of various markers and the analysis of surface phenotype of T cell clones with defined functional properties. While the study of T cell clones has clearly pointed out the inadequacy of most markers commonly used for identifying functional subsets of T cells, it provides a valuable tool for identifying new markers that may indeed be selective for a given T cell function.

Antibodies, Monoclonal↗
PubMedDate not supplied

Analysis of CD3-associated molecules in CD4- 8- human T cell clones lacking the typical alpha/beta T cell receptor.

Four clones were isolated from CD3+ 4- 8- normal peripheral blood T lymphocytes. They lacked expression of the typical alpha/beta T cell receptor, as assessed by reactivity with the WT31 monoclonal antibody (mAb) recognizing a non-polymorphic structure of the alpha/beta heterodimer. All the four clones lysed the natural killer-sensitive K562 target cells and released interleukin-2 following stimulation with phytohemagglutinin. After cell treatment with the cross-linking agent dithiobis-succinimidyl-propionate, molecules immunoprecipitated with an anti-CD3 mAb were represented by a major 45-kD and a minor 43-kD band. These molecules were different from typical alpha/beta molecules and are likely to represent the molecular product of the human gamma gene.

Antigens, Differentiation, T-Lymphocyte↗
PubMedDate not supplied

Intraperitoneal infusion of interleukin-2 in patients with malignant ascites: phenotypic and functional effects on tumor-associated lymphocytes.

The aim of the present study was to evaluate the effects of intraperitoneal interleukin-2 (IL-2) infusion on tumor-associated lymphocytes (TAL) and peripheral blood lymphocytes (PBL) in patients with malignant ascites. Six patients were given IL-2 daily for 14 days by intraperitoneal infusion using a delivery system. TAL were isolated from the ascitic fluid before (day 0) and 7 and 14 days after the initiation of the treatment. Although no variations were observed in cytolytic activity and surface markers of PBL, TAL showed an important increase in the percentage of cells expressing IL-2 receptors of lymphokine-activated killer (LAK)-1 antigen (i.e., a surface molecule expressed by human LAK cells and their precursors). Perhaps more importantly, a sharp increase of natural killer activity and the de novo generation of LAK activity were also observed.

Ascites↗
PubMedDate not supplied

Interleukin-2-induced proliferation of CD4-CD8- human thymocytes. In vitro expression of CD3 and CD8 antigens and cytolytic activity.

Human thymocytes lacking both CD4 and CD8 differentiation antigens were prepared by treating total thymocyte suspensions with a mixture of anti-CD4 and anti-CD8 monoclonal antibodies and complement. The resulting populations contained less than 2% CD4+, CD8+ or WT31+ cells and variable percentages (less than 20%) of CD3+ cells. These cell populations were cultured in recombinant IL-2 in the presence of peripheral blood mononuclear cells as feeder cells. Cells underwent extensive proliferation accompanied by a progressive increase of CD3+ and CD8+ cells. On the other hand, appearance of neither WT31+, alpha/beta-positive T cell receptor (TCR), nor CD4+ cells could be observed in several independent experiments. Functional analyses revealed the appearance and the progressive increase of cytolytic activity against the natural killer (NK)-sensitive K562 cells as well as the NK-resistant fresh melanoma cells. Experiments of T cell cloning indicated that both the expression of CD8 and CD3 antigens and the appearance of cytolytic activity were consequent to cell maturation occurring at the level of CD4-CD8- non-cytolytic cell precursors. In these experiments, more than 30% of cells underwent clonal expansion and all the clonal progenies obtained displayed cytolytic activity and expressed the CD3+WT31- surface phenotype. The expression of CD8 was variable, whereas no CD4+ clones could be obtained. Cells expressing such surface phenotype are known to belong to the TCR gamma-positive T lymphocyte subset lacking the typical alpha/beta TCR and thus appear to be the only T cell type capable of in vitro proliferation and maturation under easily reproducible culture conditions.

Antigens, Differentiation, T-Lymphocyte↗
PubMedDate not supplied

Phenotypic and functional heterogeneity of human T cell clones producing gamma-interferon.

Human T cell clones were derived from peripheral blood and screened for their ability to release gamma-interferon (gamma-IF) following PHA stimulation. Nine clones producing more than 20 U/ml of gamma-IF were expanded and analyzed for cytolytic activity in a lectin-dependent assay and for the ability to release interleukin-2 (IL-2). In addition, clones were analyzed for T4 and T8 antigen expression. Five out of nine clones had cytolytic T lymphocyte activity, while four released relatively large amounts of IL-2. Five clones were T4+ while the remaining expressed the T8+ phenotype. These results clearly indicate that gamma-IF production is not restricted to T cell subsets defined according to either functional or phenotypic criteria.

Clone Cells↗