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Biomedical subjects

L Boumsell

Publications and source records attributed to L Boumsell.

At least 127 records · Page 7Linked to original sources

The heterogeneity and functional capacities of human thymocyte subpopulations.

Analysis of human thymocytes with monoclonal antibodies belonging to five distinct clusters of differentiation (CD1, CD3-CD5, CD8) revealed a high degree of phenotypic heterogeneity. Six subpopulations could be defined in the thymic compartment characterized by the presence of CD1 antigens (cortical type); four subpopulations could be defined in the compartment characterized by the lack of CD1 but by the presence of CD5 antigens (medullary type); two subpopulations could be defined in the compartment characterized by the lack of both CD1 and CD5 antigens. Thymic samples could be categorized as either high responder or low responder to phytohemagglutinin alone. The defect of low responders was, to a large extent, attributable to a lack of interleukin 2 availability in the medullary type compartment. Yet, cortical-type subpopulations, both from high and low responders, were able to respond to phytohemagglutinin alone to the same extent. Undesirable cell contamination was excluded by limiting dilution analysis. Moreover, cortical-type cells were found to be able to respond to concanavalin A alone, while medullary-type cells and total populations did not respond to concanavalin A alone. Thus, the human thymus includes a number of cell subpopulations involved in complex functional interactions.

Antibodies, Monoclonal↗

Preferential elimination of NK and CTL functions by anti-D44 monoclonal antibody.

Monoclonal antibodies reactive with T cells at various stages of maturation were used in negative selection experiments to study their effects on NK function in the presence of complement. Anti-D47 and anti-A50, respectively, directed against corticothymocytes and mature peripheral E+ cells were without effect. Anti-D66 reactive with an epitope of the T cell E receptor inhibited up to 60% of NK activity. Anti-D44, which primarily recognizes corticothymocytes and 60 to 80% of the E(+)-PBL was found to abrogate NK activity together with alloreactive CTL reactivity but to leave intact most of the MLR and PHA proliferative responses. Therefore D44 appears as a discrete antigen allowing preferential elimination of NK cells and CTL from PBL.

Antibodies, Monoclonal↗

A novel human leukocyte differentiation antigen: monoclonal antibody anti-D44 defines a 28 Kd molecule present on immature hematologic cells and a subpopulation of mature T cells.

Anti-D44 is a cytotoxic IgG2b monoclonal antibody (MAb), which reacts with two polypeptides of 28 and 30 Kd from human peripheral T cells after western blotting. The antigen is present in low density on bone marrow cells from the myeloid lineage, probably including most CFU-GM; the antigen is present on megakaryocytes but is not detectable on erythroid cells as well as pre-B and B cells. Growth of BFU-E appears to be partially inhibited after treatment with anti-D44 + complement, an effect that should be due to bone marrow T cells rather than to BFU-E destruction. With maturation, the antigen is barely detectable on mature polymorphonuclear neutrophils, and is not detectable on platelets and monocytes. In contrast, cells from the thymic cortex carry a high density of this molecule; medullary thymocytes carry a low density. Large thymocytes ("thymoblasts") distinct from epithelial or interdigitating cells also bear a high density of the antigen. In the periphery, a subpopulation of T cells displays a high density of D44 molecules. D44 antigenic density is not linked to cell growth or to T cell activation. Double labeling and cell sorting experiments have shown that 40% of E rosette-forming cells are D44(+)-CD4+, 10% are CD8(+)-D44+ and 10% are CD4(-)+CD8-, CD2+. In an accompanying report, correlation is shown between expression of the D44 defined molecule on T cell subpopulations and the function they exert. Immunoperoxidase studies of skin, brain, and kidney tissues, facilitated by the fact that the antigen is resistant to inclusion in Epon, which permits staining of semi-thin sections, have not revealed any positive nonhematologic cell.

Animals↗

Anti-D47: a monoclonal antibody reacting with the secretory cells of human eccrine sweat glands.

Anti-D47 is a monoclonal antibody reacting with a surface antigen of human cortical thymocytes (different from the T6 antigen). It was prepared by immunization of mice with human thymocytes. The known cross-reactivity of monoclonal antibodies prepared against thymic cells with skin components prompted us to test anti-D47 on human skin as well as animal tissues. No labelling was observed on animal tissues. On human skin, anti-D47 was found to react with the secretory portion of eccrine sweat glands (ESG), i.e. with a cytoplasmic antigen of the secretory cells lining the deep portion of ESG glomeruli. No labelling was observed on apocrine sweat glands or on the excretory portion of ESG. Anti-D47 was also tested on histologically proven extramammary (vulvar) Paget's disease and basal cell epitheliomas: no staining of the neoplastic cells was observed. Anti-D47 appears to be an immunological marker of the secretory cells of human ESG and a new tool for the investigation of human sweat gland pathology.

Animals↗

[Fall in the levels of circulating lymphoblasts caused by intravenous administration of the A50 monoclonal antibody in a patient with acute T-cell lymphoblastic leukemia. A step in the demonstration of serotherapy with monoclonal antibodies].

In an 8-year-old boy with acute lymphoblastic leukaemia not previously treated intravenous administration of a single 8 mg dose of a monoclonal antibody that recognizes an epitope restricted to the surface of mature T-cells resulted, within 20 hours, in a fall in circulating lymphoblasts from 200 000 to 70 000. No adverse clinical or biological reaction was detected and no antigenic modulation occurred at lymphoblast surface. This observation constitutes a first step in the complex development of effective serotherapy for malignant diseases, using monoclonal antibodies.

Animals↗

[Identification of lymphocyte populations producing alpha-interferon by monoclonal antibodies].

Two different leucocyte populations producing alpha-interferon can be defined by monoclonal antibodies. One non glass adherent population produces interferon after induction with Herpes and Sendaï viruses. It is characterized by anti-D44 antibody, defining both some T and NK cells, but not by anti-D66 antibody with selective reactivity for T cells. The other glass adherent population is identified by OKM1 antibody, which defines about 70% of the monocytes, and can be induced only with Sendaï virus.

Antibodies, Monoclonal↗

Phenomenon of human T cells rosetting with sheep erythrocytes analyzed with monoclonal antibodies. "Modulation" of a partially hidden epitope determining the conditions of interaction between T cells and erythrocytes.

Anti-D66 is a monoclonal antibody able to inhibit E-rosette formation of T cells both at 4 degrees C and at 37 degree C but that does not inhibit T cell rosette formation with neuraminidase or 2-amino-ethylisothiouronium bromide (AET)-pretreated E. As demonstrated by capping experiments, it defines an epitope, D66, that is directly involved in E-rosette formation. D66 is distinct from the epitope defined by 9.6 because 9.6, a previously defined "pan-T" monoclonal antibody, inhibits E(AET) rosette formation and because no cross-blocking occurred between both antibodies fixation. However, 9.6 and D66 are carried by the same molecule, as demonstrated by sequential immunoprecipitation assays performed on two different T cell lines. On the thymocyte surface, also, 9.6 and D66 are most probably carried by the same molecule, as indicated by cocapping and colysostripping experiments. D66 is present at higher densities on thymocytes and activated T cells than on peripheral blood T cells. Investigation of numerous T cell populations, both normal and malignant, showed a straightforward correlation between elevated D66 density and ability to form 37 degrees C stable E-rosettes. Neuraminidase treatment of thymocytes and peripheral blood lymphocytes forming E-rosettes unmasked a large fraction of D66 not readily accessible on their surface. These hidden D66 epitopes appear to be responsible for a surprising observation: the ability of anti-D66 to inhibit E-rosette formation could be totally reversed by fixation on anti-D66 of an antibody to mouse immunoglobulin or an Fab fragment anti-mouse immunoglobulin. This would induce microdisplacement with emergence of hidden D66, as documented by fluorometric studies. Finally, malignant T cells with a differentiative status of mature T cells, but forming no (or low numbers of) E-rosettes, could be induced both to display D66 and to form E-rosettes by neuraminidase treatment.

Animals↗

The correlation of adenosine deaminase and purine nucleoside phosphorylase activities in human lymphocytes subpopulations and in various lymphoid malignancies.

Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in normal human and in malignant lymphoid cells. Thymocytes had high ADA activity (21.2 +/- 6.8 10(3) nM/h/mg) and low PNP activity (1.2 +/- 0.6), whereas T peripheral blood lymphocytes (PBL) had low ADA activity (1.20 +/- 0.22) and high PNP activity (2.8 +/- 1.3). Moreover cortico-thymocytes had higher ADA and lower PNP levels than medullary thymocytes. A linear correlation was observed between ADA and PNP activities in both thymocytes and T-PBL. Cells from 13 patients with T acute lymphoblastic leukemia (ALL) and 10 patients with T lymphoblastic lymphoma (LL) had very high levels of ADA (respectively 13.0 +/- 5.4 and 22.8 +/- 14) and low levels of PNP (respectively 1.9 +/- 0.8 and 2.5 +/- 1.4). However no clear relationship appeared between subgroups of these T-cell malignancies defined by their patterns of surface antigens, revealed by reactivity with monoclonal antibodies, and ADA and PNP levels, and there was no correlation between the two enzymes. In contrast, cells from 31 patients with HLA-DR+ common ALL had significantly low values of ADA as compared to cells from six patients with HLA-DR- common ALL and a linear correlation was observed between ADA and PNP in cells from children with non-T, non-B ALL. These results show that specific stages of T-cell development may be characterized by the relationships and the correlation between the two enzymes and suggest that T-ALL and T-LL appear to be the group of lymphoid malignancies with a high degree of incoordination between ADA and PNP activities.

Adenosine Deaminase↗

Probing human malignant T cells with lectins: a comparison with their surface antigen patterns defined by monoclonal antibodies.

Tumor cells from 40 children and 13 adults with T cell malignancies were assessed for staining with fluorescinated peanut agglutinin (PNA) and soybean agglutinin (SBA). These cell populations had also been characterized for surface surface antigens using a series of monoclonal antibodies (Mo. Ab.) that permit an assignment of malignant cells to discrete stages of normal T cell differentiation. We had previously shown a clear correspondence between lectin- and Mo. Ab-defined cell compartments within thymuses from normal children and T cells in peripheral blood. We report here that the pattern of reactivity of malignant T cells populations with lectins correlates closely the degree of maturation, as assessed by Mo. Ab. Thus, utilization of lectins together with Mo. Ab., can be clinically useful to characterize T cell malignancies. This observation shows that, in spite of a high degree of heterogeneity of malignant T cell populations from one patient to the other, in their pattern of surface antigens, these populations seem essentially to conform to the scheme of normal T cell differentiation.

Antibodies, Monoclonal↗

Changes in surface antigens on malignant T cells from lymphoblastic lymphomas at relapse: an appraisal with monoclonal antibodies and microfluorometry.

By using a panel of monoclonal antibodies reactive with lymphoid differentiation antigens and microfluorometry, we investigated the malignant cells from five patients with T-cell lymphoblastic lymphoma both at initial involvement and at relapse. We have observed changes in cell surface antigens densities in four of the five cases. These changes could be interpreted as a shift in the status of differentiation of the malignant cells. In two cases the malignant cells appeared to be arrested at an earlier stage at relapse than at initial involvement, while in the two other cases, cells at relapse appeared to be arrested at a later stage than at initial involvement. Interestingly, a parallelism was observed between regression of the differentiative status of the malignant T cells and "leukemic conversion." These observations are also relevant to the understanding of the development of tumor resistance to chemotherapy.

Adolescent↗

Non-T, non-B lymphomas are rare in childhood and associated with cutaneous tumor.

Tumor cells from a total of 116 children with non-Hodgkin's lymphoma were studied for their pattern of reactivity with a battery of cell markers, including their capacity for spontaneous formation of sheep erythrocyte rosettes (E-rosettes), demonstration of surface immunoglobulins (SIg), and positivity with antisera against T-cell antigens, the common acute-lymphoblastic-leukemia-associated antigen (cALLa), and Ia-like antigens. Fifty-eight children (50%) had T-cell lymphomas, including all those with mediastinal tumors. Fifty children (43%) had B-cell lymphomas, including 44 of the 45 with abdominal primaries. Eight children (7%) had non-T, non-B tumors, 4 of whom presented at a young age with cutaneous lymphoblastic tumors. These results demonstrate that the great majority of children with NHL, not leukemic at diagnosis, have tumors clearly committed to either T- or B-cell differentiation pathways and only rarely exhibit the common ALL phenotype (cALLa+, Ia+, E-, T-, SIg-), contrasting with the distribution of childhood lymphoblastic leukemias. The unusual association of these non-T, non-B cases with skin involvement has not previously been reported, raising speculation regarding patterns of lymphocyte traffic and origins of childhood lymphomas and leukemias.

Adolescent↗

Syndrome of neutrophil agranulocytosis, hypogammaglobulinemia, and thymoma.

The clinical, hematologic, and immunologic findings of a syndrome of agranulocytosis, hypogammaglobulinemia, and thymoma are described. Neutrophil agranulocytosis predisposing to severe infectious disease resulted from a deficiency of mature cells in bone marrow. Autologous and heterologous stem cell growth in vitro was inhibited by the patient's serum. Immunoglobulin deficiency was secondary to the absence of peripheral blood B lymphocytes, while T-cell subpopulations and cellular immunity were present. Surgical removal of a spindle cell thymoma had no effect on the agranulocytosis and B-cell deficiency. The hematologic findings did not respond to steroid therapy and cyclophosphamide. However, the agranulocytosis improved with repeated plasmapheresis and the patient achieved a clinical remission.

Agammaglobulinemia↗

Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.

A series of monoclonal antibodies was used for the characterization of malignant T cells from 21 patients with lymphoblastic lymphoma (LL). The tumor population from these patients showed a marked degree of phenotypic heterogeneity and a proportion (one-third) of patients had tumor cells that did not conform exactly with the cells normally detected in the thymus. However, these cell populations could be related to the early or common or late thymocyte population (about one-third of the patients in each category). This contrast, with the characterization of malignant T cells from 43 patients with acute lymphoblastic leukemia (ALL) that could be related to either early or common thymocytes, with an exception of two patients categorized as having a tumor population related to late thymocytes. Further phenotypic differences between cells from ALL and LL could be demonstrated by investigation with two additional monoclonal antibodies, A50 and U4. Among patients with malignant T cells related to common thymocyte, 0/12 patients with ALL had cells recognized by A50, where 5/8 patients with LL had A50+ cells. Among patients with early thymocytes, only patients with ALL had cells recognized by U4. In addition, 5 LL patients had cells reactive with J5, a monoclonal antibody recognizing the common ALL antigen (CALLA). Since CALLA was found on cells related to common and late thymocytes, CALLA is neither lineage specific, nor can it be viewed as being peculiar to malignant lymphoid cells arrested at very immature stages of differentiation.

Adolescent↗

Correspondence between lectin-defined and surface antigen-defined cell subpopulations in the human thymus: its variation during ontogeny.

In the thymus of children, congruent to 50% of cells are recognized both by peanut agglutinin and soybean agglutinin (PNA+, SBA+), congruent to 23% of cells are PNA-, SBA-, and 23% are PNA-, SBA+. This pattern of recognition was compared with the reactivity of these cells with monoclonal antibodies recognizing T cell differentiation antigens A 50 and a series (T3, T6, T8) that defines 3 discrete stages of T cell differentiation. Most PNA+, SBA+ display T6 and T8 but not T3 antigens; most PNA-, SBA+ display T3+ and A 50+ but not T6; and T3-, T6-, A 50- cells are PNA-, SBA-. Thus, there is a close correspondence between PNA+, SBA+ cells and the common (cortical) T3-, T6+ thymocytes; between PNA-, SBA+ cells and late (medullary) T3+, T6- thymocytes; and between PNA-, SBA- cells and early thymocytes. During ontogeny, although there are fewer PNA+ cells in the thymus, the proportion of T3+ cells, T6+ cells, and T3-, T6- cells showed no major modification as early as 16 wk.

Agglutinins↗

[Burkitt's type acute lymphoblastic leukemia. Cellular phenotype and chromosome abnormally (author's transl)].

A 13 year-old boy presented with Burkitt's type acute lymphoblastic leukemia (B-ALL). Studies of immune markers on his lymphoblasts suggest they have reached a fairly advanced level of differentiation with in the B-cell lineage. Presence of 1q+ and 8q- chromosomes suggest an unusual (1;8) translocation and is in agreement with current concepts concerning the frequent chromosome 8 changes in B-ALL.

Adolescent↗

Surface antigens on malignant Sézary and T-CLL cells correspond to those of mature T cells.

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T-cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sézary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T-chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Antibody Specificity↗