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Biomedical subjects

L Boumsell

Publications and source records attributed to L Boumsell.

At least 73 records · Page 4Linked to original sources
PubMed1993

Significant enlargement of a specific subset of CD3+CD8+ peripheral blood leukocytes mediating cytotoxic T-lymphocyte activity during human immunodeficiency virus infection.

We have obtained a monoclonal antibody termed BY55 that defines an 80-kDa cell-surface structure on a subset of circulating peripheral blood mononucleocytes. This structure, which was not detected on most cell lines or activated lymphocytes, was expressed exclusively on 15-25% of CD2+ circulating lymphocytes, including a major subset within the CD3- and the T-cell receptor gamma delta + lymphocytes and a small percentage of the CD3+CD8+ cells. Moreover, we have shown that the BY55 molecule delineated the competent killer circulating lymphocytes. In the present report, additional two- and three-color immunofluorescence studies of peripheral blood lymphocytes were done to precisely determine BY55 expression within the T-cell population. In normal individuals, peripheral blood CD3+CD8+BY55+ cells represented only 5-6% of the lymphocytes, and these cells possessed cytolytic activity. Interestingly, we found that the percentage of total BY55+ lymphocytes as well as the percentage of CD3+CD8+BY55+ was significantly increased in peripheral blood lymphocytes of human immunodeficiency virus-seropositive individuals.

Antibodies, Monoclonal↗
PubMed1993

A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity.

Human lymphocytes with natural killer (NK) activity, including most activated gamma/delta+ T lymphocytes, recognize and lyse tumor target cells without requiring recognition of major histocompatibility complex antigen. However, unlike gamma/delta+ T lymphocytes, NK cells do not express CD3/T cell receptor (TCR) molecules, and the receptors involved in cell-mediated cytotoxicity are unknown. To further delineate circulating NK cells, we developed monoclonal antibodies (mAbs) against the human NK leukemia YT2C2. We report the isolation of a mAb termed BY55, recognizing at the cell surface a novel 80-kD protein with restricted expression. In addition to the immunizing cell line, this mAb binds to circulating NK cells, gamma/delta+ cells, and a minor subset of alpha/beta+ T lymphocytes. Expression of the BY55 mAb-reactive epitope/molecule is regulated by activation, as short-term culture of peripheral blood lymphocytes (PBL) with phorbol ester induced its downmodulation. Furthermore, BY55 mAb reactivity was found neither with the NK nor with the TCR alpha/beta+ gamma/delta+ clones tested. Biochemical studies as well as phenotypic analysis revealed that this structure is different from all previously identified molecules on the lymphocyte cell surface. Interestingly, we found that BY55+ cells exert most NK activity obtained with fresh circulating lymphocytes. We report that within fresh E rosette-positive PBL only a subset of the CD16+, CD56+, and CD57+ cells coexpressed BY55 molecule, indicating that BY55 mAb defines a unique subset mediating NK activity of circulating PBL.

Antibodies, Monoclonal↗
PubMed1993

The lymphocyte surface antigen CD38 acts as a nicotinamide adenine dinucleotide glycohydrolase in human T lymphocytes.

The extracellular domain of the lymphocyte surface antigen CD38 has been recently shown to share a high sequence homology with a nicotinamide adenine dinucleotide (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod Aplysia (E. States, D.J., Walseth, T.F., Lee, H. C., Trends Biochem. Sci. 1992. 17:495). In agreement with this finding, we present here evidence that CD38-overexpressing T cells, such as human thymocytes and cells from the human HPB-ALL T cell line, exhibit a NAD(+)-hydrolyzing enzymatic activity present on the outer surface of the cell membrane. In contrast, T lymphocytes with relatively low levels of CD38 marker, such as the human Jurkat cell line, display a lower activity. This suggests a relationship between ecto-NAD+ glycohydrolase activity and CD38 expression, as confirmed here when comparing wild-type Jurkat cells and a Jurkat cell variant overexpressing the CD38 molecule. Moreover, CD38 immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase enzyme: it transforms NAD+ stoichiometrically into nicotinamide plus adenosine 5'-diphosphoribose. Altogether these results strongly support the assumption that CD38 is actually a lymphocyte-specific NAD(+)-hydrolyzing enzyme, a finding that give new prospects to understand the in vivo function of this cell membrane protein.

ADP-ribosyl Cyclase↗
PubMed1993

Immunohistochemical detection of CD1A antigen in formalin-fixed and paraffin-embedded tissue sections with monoclonal antibody 010.

The immunoreactivity of a CD1a monoclonal antibody (MAb), denoted 010, was investigated by means of the streptavidin-biotin-peroxidase method in formalin-fixed and paraffin-embedded tissues from 47 cases. The samples comprised reactive lymphoid proliferations of skin, tonsil, and lymph node including dermatopathic lymphadenopathy and Langerhans' cell histiocytosis, Hodgkin's and non-Hodgkin's lymphomas, and thymomas. Interdigitating and dermal dendritic cells, veiled cells, Langerhans' cells, and also cortical thymocytes and their neoplastic counterparts displayed immunostaining with MAb 010 in paraffin sections. These results are identical to previous ones reported for other CD1a MAbs in fresh or frozen specimens. The findings suggest that the binding site of 010 is a fixation-resistant epitope of CD1a antigen which has not been previously identified.

Antibodies, Monoclonal↗
PubMed1993

Identification of a novel functional 85-kD glycoprotein restricted to long-term dividing human lymphocytic lines.

Lymphocyte activation induces or increases the expression of several surface structures, some of which are directly involved in cell growth such as receptors for IL2 or transferrin. To identify new structures characteristic of activated lymphocytes, we developed a series of mAbs against functionally defined human T-cell clones or the NK-mediating cell line YT2C2. In this study, we report the isolation of an mAb termed AY19 recognizing, at the cell surface, an 85-kD glycoprotein whose expression is restricted to T-lymphocyte clones, leukemic T-cell lines, and T-ALL peripheral blood cells. Biochemical studies, as well as phenotypic analysis, revealed that this structure is different from all previously identified molecules on the cell surface of lymphocytes. Furthermore, functional studies showed that triggering of this 85-kD structure on cloned T-lymphocytes through the AY19 epitope led to an inhibition of CD3-induced proliferation. These findings suggest that the AY19 mAb defines a T-cell antigen expressed mainly on long-term dividing lymphocytes and, therefore, its putative ligand might play a role in the regulation of T-lymphocyte growth induced by CD3-TcR stimulation.

Animals↗
PubMed1993

Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg).

IVIg are increasingly used for the treatment of autoimmune diseases. In the present study, we show that IVIg contain antibodies directed against CD5, a cell surface molecule of T cells which is also a marker of the autoantibody-producing CD20+ ('B-1') subset of B lymphocytes. Antibodies to the CD5 molecule were demonstrated in IVIg by the ability of therapeutic preparations of IVIg to inhibit the binding of labelled CD5 MoAb to the CD5-expressing human T cell line H9. Preincubation of H9 cells with IVIg or with F(ab')2 fragments prepared from IVIg resulted in dose-dependent inhibition of the binding of CD5 antibody. The presence in IVIg of antibodies to the CD5 molecule was further confirmed by the binding of IVIg to mouse L cells that expressed human CD5 molecules following a stable transfection with CD5 cDNA. Human CD5 antibodies in IVIg provide therapeutic immunoglobulin preparations with the potential of modulating T cell functions through CD5, and of regulating the expression of B cell subsets expressing CD5. This may have implications for the treatment of autoimmune diseases.

Animals↗
PubMed1993

Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.

GM-CSF has been shown to be important for the survival and function of cells of dendritic cell/Langerhans cell (LC) lineage in vitro. Since these cells have been demonstrated to infiltrate human lung and some lung carcinomas, we hypothesized that the production of GM-CSF in the lung could be important in their recruitment and differentiation. Using both immunohistochemistry and in situ hybridization, we have shown that: (a) GM-CSF was produced by normal bronchiolar epithelium, the only site were CD1a+ LC are observed in the normal lung, whereas neither GM-CSF production nor LC were identified in normal alveolar epithelium. (b) In inflamed pulmonary tissue, hyperplastic alveolar cells produced GM-CSF, and CD1a+ LC accumulated adjacent to these cells. (c) Some, but not all, lung carcinomas produced this cytokine, and a close correlation was found between the production of GM-CSF and the number of CD1a+ LC infiltrating these tumors. Since GM-CSF was produced at all sites where CD1a+ LC are known to accumulate, but not at other locations within the lung, these data suggest that the local production of GM-CSF by certain lung cells may play an important role in determining the distribution and differentiated state of dendritic cell/LC in the human lung.

Adenocarcinoma↗
PubMed1992

Increased surface expression of a newly identified 150-kDa dimer early after human T lymphocyte activation.

Lymphocyte activation induces or increases the expression of several surface structures, some of which are directly involved in cell growth such as receptors for IL-2 or transferrin. In order to identify new structures characteristic of activated lymphocytes, we developed a series of mAb against functionally defined human T cell clones. In the present study we report the isolation of a mAb termed BB18 recognizing, at the cell surface, a novel 150-kDa glycoprotein dimer whose expression on T lymphocytes increases readily after their activation with various stimuli including lectins. In contrast, in the presence of PMA, cell-surface expression of this 150-kDa structure is down-regulated even earlier than CD3 molecules. Biochemical studies as well as phenotypic analysis revealed that this structure is different from all previously identified molecules on the lymphocyte cell surface. Furthermore, functional studies showed that triggering this disulfide-linked dimer through BB18 epitope in the presence of submitogenic concentrations of PMA induced strong lymphocyte proliferation. This proliferative response require E+ cells and accessory cells, and this even after immobilization of BB18 mAb.

Animals↗
PubMed1992

The CD39 molecule defines distinct cytotoxic subsets within alloactivated human CD8-positive cells.

Lymphocyte activation induces or increases the expression of several surface structures, none of which is characteristic of an activated cell subset. In particular, structures such as CD45RO, CD25, CD26, CD49b, CD54, CD71 are expressed by the vast majority of lymphocytes at various times following in vitro activation. CD39 molecules were originally identified on activated B lymphocytes and have recently been described on activated T cell clones. In the present report, we have characterized phenotypically and functionally defined cell subsets generated during an in vitro allostimulation. Results indicated that the percentage of CD39+ cells reached a maximum at day 6 and remained stable thereafter. We demonstrate that CD39 expression allows the identification within the allosensitized CD8+ cytotoxic cells of distinct subsets of cells mediating allo cytotoxic T lymphocyte or natural killer (NK)-like reactivity. More precisely, CD8+CD39+ alloactivated cells mainly mediate specific killer activity, whereas CD8+CD39- alloactivated cells predominantly exhibit NK-like reactivity. Further, we show a high functional correlation associated with the lack of CD39 expression on NK-like alloactivated CD8+ cells, while there is no association with CD56 or CD57 NK-associated structures.

Adenosine Triphosphatases↗
PubMed1992

TCR gamma delta bearing T lymphocytes infiltrating human primary cutaneous melanomas.

In situ immunophenotypic studies show that tumor infiltrating T lymphocytes from six of 11 fresh cutaneous primary melanomas tested contain T-cell receptor gamma delta expressing cells whereas those from 8 metastatic melanomas did not. In three cases these cells represent an unexpectedly high proportion of the lymphocytic infiltrate, ranging from 15 to 25%. This elevated percentage is maintained when tumor infiltrating lymphocytes are propagated in vitro for 2 or 3 weeks in the presence of recombinant interleukin 2 and autologous tumor cells. Functional studies reveal that gamma delta lines or clones developed from lymphocytes infiltrating primary melanoma display, in addition to their natural killer-like activity, a potent autologous tumor cell cytotoxic activity that does not seem to be restricted by major histocompatibility complex gene products.

Humans↗
PubMed1991

Proliferation of resting lymphocytes is induced by triggering T cells through an epitope common to the three CD18/CD11 leukocyte adhesion molecules.

LFA-1, Mac-1, and p150,95 are a family of functionally important leucocyte integrins that share a common beta-subunit and participate in cellular adhesion. Monoclonal antibody to LFA-1 were described to block T-cell-mediated killing by inhibiting adhesion to target cells and to decrease T cell responses by preventing cell-cell contact. Recently it was demonstrated that LFA-1 molecule was involved in signal transduction. We report here that a monoclonal antibody termed 6.7 reacting with the three members of the leucocyte integrins is able in the presence of monocytes to directly induce the proliferation of resting peripheral blood T cells obtained from normal individuals. These results suggest the possibility that LFA-1 molecules could trigger T lymphocyte activation in addition to their role in homing, growth, and differentiation.

Antibodies, Monoclonal↗
PubMed1991

Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases.

'Very late antigen' (VLA) proteins are members of the integrin superfamily with cell-surface receptor function and are involved in the cell-cell matrix interaction. They are heterodimers with a common beta 1 chain and different alpha chains counted through VLA-1 to VLA-6. The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor. Using monoclonal antibodies and an indirect immunoperoxidase method, we investigated the expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in 20 normal colonic mucosa samples, in 20 colonic adenomas, and in 96 carcinomas together with 10 accompanying liver metastases. All three proteins were expressed throughout the colonic epithelium, except for VLA-alpha 2, which was present in the cryptic gland but was absent on the mucosal surface in some cases. In general, adenomas were strongly positive for the VLA proteins but 3 of 20 cases showed focal VLA-alpha 2-negative areas. The carcinomas revealed considerable heterogeneity of VLA-alpha 2 expression; ie, 59 tumors were completely positive, 35 tumors revealed a focal loss of antigen, and 2 cases were negative. This reduced antigen expression was statistically associated with Dukes' stage C/D (P = 0.003). VLA-alpha 6 was expressed throughout in all tumors. VLA-beta 1 was found extensively expressed in 77 carcinomas, partially expressed in 17 carcinomas, and was absent in 2 carcinomas. As compared to their primary tumors, liver metastases showed roughly corresponding patterns of antigen expression. The down regulation/loss of VLA proteins in a subset of epithelial colon tumors might cause a disturbed cell-cell/cell-matrix interaction that might augment the invasive property of their cells.

Adenoma↗
PubMed1990

In vitro differentiation from a pluripotent human CD4+CD8+ thymic cloned cell into four phenotypically distinct subsets.

Human thymic cell differentiation is almost totally unknown. In the present study we developed an in vitro system using human thymic cloned cells to analyze precursor-progeny relationship. We obtained several CD4+CD8+ double positive thymic clones that could give rise after several weeks in culture only to either CD4 or CD8 single positive clones. By contrast we isolated a unique pluripotent thymic double positive clone, termed B12, which differentiated into four phenotypically distinct T cell clones, namely double-positive CD4+CD8+, double-negative CD4-CD8- or either single-positive phenotype. We derived stable subclones representative of each phenotype and we showed by molecular analysis that they expressed the same TCR. Utilization of either CD3 or anticlonotypic mAb revealed that this TCR expressed by the four subclones was functional.

Antigens, CD↗
PubMed1990

CD1 stimulation of human T cell lines induces a rapid increase in the intracellular free Ca2+ concentration and the production of IL-2.

The effect of a battery of CD1 mAb on intracellular free Ca2+ concentration and IL-2 production has been examined on different T cell lines in this study. Both 0249F and NU-T2 two CD1b specific mAb tested, induced a rapid increase in the intracellular Ca2+ concentration on HPBALL T cells whereas only one (L161) among three different CD1c mAb (L161, 10C3, and M241) produced a similar effect. In contrast the addition of four different CD1a mAb directed against two different epitopic groups of this molecule were uneffective in modifying the intracellular Ca2+. Both L161 and 0249F also induced a comparable increase in the intracellular Ca2+ concentration on MOLT 4 and JURKAT, two other T cell lines of similar phenotype. The effect of L161 mAb on the IL-2 production of the IL-2 producing T cell line JURKAT was also examined. The association of the latter with PMA strongly induced the production of IL-2 on this cell model while either L161 or PMA alone had no effect. Although the natural ligand and the function of CD1 molecules are still unknown, the accumulation of these data strongly suggest that CD1b and CD1c might represent two activatory pathways for immature T cells operating before the classical CD2 and CD3 activation pathways.

Antibodies, Monoclonal↗
PubMed1990

Study of the CD3-associated T-cell receptors reveals further differences between T-cell acute lymphoblastic lymphoma and leukemia.

We show further differences between two clinically related entities, T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), by using several monoclonal antibodies (MoAbs) reacting with either constant or variable regions of T-cell receptors (TcR) alpha beta and gamma delta or with various CD molecules. We analyzed a panel of 15 T-ALL and 15 T-LL selected for their cell surface expression of the CD3 molecules. The results indicated that TcR gamma delta is more frequently used than TcR alpha beta in T-ALL (10 of the 15 patients tested). This is in contrast to the results obtained with T-LL where the vast majority expressed TcR alpha beta (13 of the 15 patients). These findings suggest that the leukemic cells could have a different origin in these two diseases. In addition, analysis of TcR variable regions expressed by the leukemic blasts showed that, in most cases, they had rearranged functional V delta 1 gene segments (8 of 11 patients), whereas in a unique case V delta 2 gene segment was used. Together, these results and those indicating that T-ALL cells coexpress the CD1a, b, and c molecules strengthen the possibility that although these leukemic cells express the CD3-TcR complex at their cell surface, their normal counterparts are not found in peripheral blood.

Antibodies, Monoclonal↗
PubMed1990

Identification of a novel 110-kilodalton structure expressed on a subset of T cell receptor-gamma delta-bearing cloned lymphocytes.

A small percentage of circulating CD3+ cells express a heterodimeric gamma delta receptor. Most of these cells do not express the surface marker CD4 and only a fraction of them bear CD8 molecules. The specificity and function of TCR-gamma delta are unclear. We obtained a murine mAb produced against an IL-2-dependent human T cell clone defining a novel molecule sTA which is not expressed on resting human peripheral blood CD3+ cells but strongly expressed on a fraction of TCR-gamma delta-bearing clones. Like receptors for growth factors such as IL-2, the sTA Ag is present on clones and cell lines according on the cell cycle. SDS-PAGE analysis of sTA immunoprecipitates from 125I-labeled sTA+ clone lysate demonstrated a single band of molecular mass 110 kDa under reducing conditions. Triggering with anti-sTA mAb did not result in [Ca2+]i mobilization of sTA+ clones. Additionally, the presence of anti-sTA did not alter the cytotoxicity of these sTA+ clones neither against tumor target cells nor against specific PHA blast cells. Interestingly, due to the fact that most sTA+ clones fail to proliferate in response to CD3 triggering, it appears that sTA may serve as a useful marker to study the functional heterogeneity of TCR-gamma delta expressing cells.

Antibodies, Monoclonal↗
PubMed1990

Selective induction of autocytotoxic activity through the CD3 molecule.

In the present study we show that when certain major histocompatibility complex-alloreactive CD8+ T cell clones with natural killer-like activity are stimulated through their CD3 molecules, in the absence of significant cross-linkage (as provided by Fab' fragments of OKT3 antibodies) they lose their interleukin 2 response. This is attributable to an induction of a nonspecific autocytolytic activity. These results suggest that activation of this process in some cytotoxic cells leads to an overall decrease in CTL activity and constitutes a possible mechanism of suppression of the immune response.

Antigens, CD↗