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L Boumsell

Publications and source records attributed to L Boumsell.

At least 109 records · Page 6Linked to original sources
PubMed1987

Regulation of helper T cell clone proliferation via the CD2 molecule.

We have investigated the requirements for CD2-induced proliferation of a CD4+, CD8-, CD3+, CD2+ antigen-specific, class II-restricted proliferating cloned cell line. A combination pair of two monoclonal antibodies (MoAb) recognizing, respectively, TII1 and D66 epitopes on the CD2 molecule was used as a stimulus. The regulatory function of accessory cells and various interleukins in this proliferation was determined. The results show that although this clone was able to proliferate in the absence of accessory cells (AC) or interleukin 1 (IL-1) when stimulated by these MoAb, AC constantly enhanced the response to these MoAb. AC acted by increasing high-affinity IL-2 receptor expression. On the contrary they did not play any role in IL-2 production. This regulation of IL-2 receptor expression by AC was specific of adherent cells, did not involve Fc receptors, was impaired when AC were metabolically inactivated and did not require T cell-AC interaction via LFA1, CD4, or HLA molecules. The AC function was not abrogated by anti-IL-1 antibodies and could not be replaced by exogenous IL-1. These results were compared to previously described AC effects on resting T-cell proliferation when stimulated with the same pair of anti-CD2 MoAb. Clear differences in activation requirements in resting and activated T cells via CD2 molecules were found.

Antibodies, Monoclonal↗
PubMed1987

Three different erythrocyte surface molecules are required for spontaneous T cell rosette formation.

We have obtained three anti-sheep erythrocyte (E) monoclonal antibodies (MAb) which block rosettes with human T cells. They also block rosettes with E from all the species we have tested, including rosettes with autologous E. They define three different minor components on the E surface: MAb N217 precipitates a single 42-kilodalton (kDa) chain and MAb N4 a single 14-kDa chain, and MAb N23 immunoprecipitates under nonreducing conditions a single band at approximately 220 kDa, which is resolved under reducing and alkylating conditions, in two bands migrating at approximately 110 kDa and approximately 220 kDa. Thus MAb N23 is likely to react with a complex made of covalently linked 100-kDa chains associated in a noncovalent fashion with approximately 220 kDa chains. In addition, we have observed a puzzling phenomenon, i.e., that binding the MAb N23 first increases, to a large extent, the amount of N4 epitopes which can be subsequently detected on E. This effect was not observed when N217 MAb or antiglycophorin (either monoclonal or polyclonal) antisera were first bound on E. Therefore the N23 and N4 molecules must interact on the E surface. This finding discloses the complex interactions between the T cell and E surface component that must occur in the process of rosette formation, including that with autologous E. These observations are of interest in view of the recent evidence that the CD2 molecule is involved both in adhesion and activation aspects of T cell functioning.

Antibodies, Monoclonal↗
PubMed1987

Role in T-cell activation for HLA class I molecules from accessory cells: further distinction between activation signals delivered to T cells via CD2 and CD3 molecules.

The immunological function of major histocompatibility complex molecules, including HLA class I molecules, is to present antigens and/or their processed peptides to various lymphocyte subpopulations. Thus, they play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. We looked for a role of major histocompatibility complex molecules during T-cell activation induced by monoclonal antibody (mAb) or combinations of mAb recognizing the two well-characterized T-cell surface molecules CD3 and CD2. To activate T-cell peripheral blood lymphocytes, we used a CD3 mAb or two different pairs of CD2 mAb, CD2 "GT2 + T11(1)" and CD2 "D66 + T11(1)," which, as we have previously shown, deliver different signals of activation to T cells. Anti-HLA class I mAb blocked the activation induced by CD3 mAb or by CD2 GT2 + T11(1), but it did not block activation induced by CD2 D66 + T11(1). We observed this pattern of inhibition according to the stimulus used to activate T cells both when the anti-HLA class I mAbs were added to cultures of whole peripheral blood mononuclear cells and when they were fixed to monocytes only. In the latter case, purified monocytes were first incubated with the anti-HLA mAb (whether whole immunoglobulin or Fab fragment) and then fixed with paraformaldehyde before culture with autologous purified T cells. Anti-HLA class I fixed on monocytes prevented both interleukin 2 (IL-2) receptor expression and IL-2 synthesis on T cells. The inhibitory effects of anti-class I mAb bound to monocytes were not reversed by adding large amounts of recombinant IL-2 or recombinant IL-1, a finding consistent with the observations that accessory cells surface components can fully complement the signals directly delivered to T cells by CD2 or CD3 mAb. We conclude that HLA class I from accessory cells plays an important role in the early phase of T-cell activation when direct contacts between accessory cells and T cells are required.

Antibodies, Monoclonal↗
PubMed1987

[Implication of HLA class I molecule from monocyte in T-cell activation by CD2 or CD3 monoclonal antibodies].

The role of monocytes in human T-cell activation by monoclonal antibodies (mAb) recognizing CD3 molecule or by 2 mAb pairs directed against different epitopes of CD2 "GT2+T11(1)" or "D66+T11(1)" has been studied. It appears that HLA-cl I molecules from monocytes are involved in the early activation phase of T-cells stimulated by CD3 or CD2 when direct contacts between T-cells and monocytes are required. Thus, pretreatment of monocytes with HLA-cl I mAb inhibited IL 2 receptor appearance and IL 2 synthesis on T-cells stimulated by CD3 mAb or CD2 "GT2+T11(1)" mAb pair.

Antibodies, Monoclonal↗
PubMed1987

Analysis of CD1 molecules on thymus cells and leukemic T lymphoblasts identifies discrete phenotypes and reveals that CD1 intermolecular complexes are observed only on normal cells.

We looked at the surface expression of the three distinct human thymic cell surface differentiation antigens, CD1a, CD1b, and CD1c, that presently define the first cluster of differentiation (CD) on the cells from 34 patients with acute T cell malignancies. We also studied the expression of other T cell-restricted molecules, including the T cell receptors, on these cells. Our results confirm the extensive phenotypic heterogeneity of the cells from acute T cell malignancies, which contrast with the more limited phenotypic diversity of subacute or chronic T cell malignancies. Our study of normal children and fetal thymus cells shows that the extensive phenotypic heterogeneity of the malignant cells reflects the heterogeneity of the thymic subpopulations and shows that most of the phenotypes observed on malignant T cells have a normal counterpart, particularly in the fetal thymus. Moreover, we demonstrate that the CD1a molecules, which can form three different types of noncovalent intermolecular complexes on the surface of normal thymus cells, do not form any noncovalent intermolecular complexes on the surface of leukemic cells. We also show that CD1a molecules can form covalent intermolecular complexes with CD8 molecules on some but not all malignant cells.

Antibodies, Monoclonal↗
PubMed1986

T cell activation via CD2 [T, gp50]: the role of accessory cells in activating resting T cells via CD2.

Monoclonal antibody (MAb) GT2 defines a unique epitope on the CD2 molecule. GT2 triggers T cell mitosis in combination with any MAb directed against 9.6/T11(1) or D66, two previously defined CD2 epitopes. We have shown already that accessory cells (AC) are required for plenary T-PBL activation by any pair of Ab directed against D66 + 9.6/T11(1). In this study, we further investigated their role and found it to vary with the anti-CD2 pair used. When purified T-PBL preparation is used, the level of [3H]TdR incorporation observed with anti-(GT2 + 9.6/T11(1)) Ab was not significant; however, it did prove significant, although greatly reduced, with the other anti-CD2 pairs tested. This was due to qualitative differences in the process of T-PBL activation, and the role of AC, because: anti-(GT2 + 9.6/T11(1)) did not induce IL 2-R expression on purified T-PBL, whereas the other anti-CD2 pairs tested did; anti-(GT2 + 9.6/T11(1)) did not induce detectable IL 2 secretion from purified T-PBL, whereas the other anti-CD2 pairs tested induced a low amount; and anti-CDw18 Ab inhibited the mitogenic effect of anti-(GT2 + 9.6/T11(1)) on PBMC by preventing both IL 2-R expression and IL 2 secretion, whereas anti-CDw18 Ab enhanced the mitogenic effect of the other anti-CD2 pairs tested. Paraformaldehyde-fixed AC fully restored, and recombinant IL 1 partially restored purified T-PBL mitosis triggered by all anti-CD2 pairs tested. To induce IL 2 synthesis, the necessity to cross-link anti-CD2 Ab was demonstrated by coupling one Ab on Sepharose beads and adding the second Ab in the soluble phase: under these circumstances, anti-CD2 pairs were mitogenic solely in the presence of AC. These data can be interpreted as follows. Most anti-CD2 pairs require minimal contact between AC and T-PBL to induce plenary levels of IL 2 synthesis. When anti-(GT2 + 9.6/T11(1)) are used, additional contact is necessary, both for IL 2-R expression and IL 2 synthesis, which would include CDw18 for stabilization. We believe these differences could be related to different conformational changes on the CD2 molecule, depending on the epitope on which the antibodies bind, and could account for different signaling to T cells.

Animals↗
PubMed1986

Heterogeneity of the first cluster of differentiation: characterization and epitopic mapping of three CD1 molecules on normal human thymus cells.

In humans, the presence of two non-HLA class 1-like molecules, whose expression, similar to murine Tla, is restricted to cortical thymocytes, has been shown with monoclonal antibodies defining the first cluster of differentiation (CD1). We report here with the use of 12 anti-CD1 antibodies and a combination of technical approaches, the characterization of a third CD1 molecule. We show that we can presently define seven different epitopes on the three CD1 molecules: four epitopes are restricted to the 49,000 dalton molecule, two epitopes to the 45,000 dalton molecule, and one epitope to the 43,000 dalton molecule. We show that the association of the newly identified 45,000 dalton heavy chain with human beta2-microglobulin is weak. In addition we show the presence of a fourth non-HLA class I molecular species on the surface of normal human thymus cells.

Animals↗
PubMed1986

Regulation of immunoglobulin synthesis by human T cell subsets as defined by anti-D44 monoclonal antibody within the CD4+ and CD8+ subpopulations.

In our previous paper, we demonstrated that anti-D44 MAb can, in the presence of complement, eliminate all the allocytotoxicity generated during a mixed lymphocyte reaction without affecting the alloproliferative response. As approximately 70% of CD4+ cells and 30% of CD8+ will be stained with anti-D44 MAb, we researched the functional role of the D44+ and D44- cells in each of these T cell subsets in the PWM-induced antibody response. We found that most of the helper activity for immunoglobulin (Ig) synthesis was mediated by CD4+ D44+ lymphocytes and that virtually all the suppressive activity was mediated by CD8+ D44- lymphocytes. Surprisingly enough, we noticed that the low level of Ig synthesis induced in B cells by CD4+ D44- lymphocytes could be strongly amplified by the addition of radiosensitive CD8+ lymphocytes, suggesting coexisting opposite immunoregulatory functions within the CD8+ T cell subset. These results, together with previous data, indicate that anti-D44 MAb subdivides T cells into subpopulations with distinct functional repertoires: a CD4+ D44+ helper subpopulation, a CD8+ D44+ cytotoxic subpopulation, and a CD8+ D44- suppressor subpopulation.

Antibodies, Monoclonal↗
PubMed1986

Control of cell proliferation within the human thymus. A very limited thymocyte subpopulation generates a suppressive activity.

It is shown here that a minor subpopulation of the human thymus, representing 2-3% of the whole thymocyte population, can suppress proliferation of syngeneic or allogeneic thymocytes to various stimuli. In contrast, this suppressor cell population has no influence on the proliferative response of peripheral blood lymphocytes. This subpopulation was defined by its cell surface phenotype as CD3+, CD1-, 4-, 8- cells. Its suppressive activity is generated after concanavalin A (Con A) stimulation, but not after stimulation with phytohemagglutinin. In addition, the suppressive activity is not modified by extensive washes of Con A-stimulated cells with 1-O-methyl-alpha-D-glucopyranoside, a specific sugar for Con A. This suppressor cell population does not exert any detectable cytotoxic activity, nor does it act by consuming available interleukin 2 (IL 2). Rather, it prevents IL 2 receptor expression on thymic target cells. Since Con A might activate T cells by binding to molecules physiologically involved in T cell activation, particularly the CD3-T cell receptor complex, these data could be relevant to the regulation of normal thymic differentiation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

A unique epitope on the CD2 molecule defined by the monoclonal antibody 9-1: epitope-specific modulation of the E-rosette receptor and effects on T-cell functions.

Monoclonal antibody (MoAb) 9-1 shows unique binding properties to CD2 resulting in peculiar epitope specific changes. 9-1 shows competitive binding with MoAb to D66 epitope, and gives a similar staining pattern with T-cell populations, at a low density on resting T cells, and high density on thymocytes and activated T cells. However, 9-1 has the opposite effect on anti-D66 MoAbs on rosette formation, namely, 9-1 increases the stability of rosettes, but 9-1 plus anti-mouse Ig bound to T-cell surface blocks rosettes. 9-1 plus anti-mouse Ig, like anti-D66 MoAbs, induces further appearance of D66 and 9-1 epitopes but, contrary to anti-D66, induces appearance of T11(3) epitopes. Thus, binding 9-1 results in unique "epitope-specific modulation" events that are not solely artificial, but appear to mimic events naturally occurring during T-cell differentiation/activation. The effects of binding 9-1 on T-cell functions also display peculiarities. 9-1, like anti-D66 MoAbs, activates T cells when added in combination with anti-9.6/T11(1) MoAbs but not with anti-T11(3). To obtain full activation, monocytes are required; however, adding 9-1 alone do not inhibit specific T-cell cytotoxicity contrary to anti-D66 or anti-9.6/T11(1), although 9-1 inhibits NK activity of peripheral cells. Given the apparent complexities of the functions exerted by CD2, these data show that definite conformational changes or reorientation, which would be naturally produced by soluble and/or cell surface ligand(s), would be key events in determining how CD2 will influence T-cell functions.

Antibodies, Monoclonal↗
PubMed1986

The human cell surface glycoprotein complex (gp 120,200) recognized by monoclonal antibody K20 is a component binding to phytohaemagglutinin on T cells.

Monoclonal antibody K20 recognizes a human glycoprotein complex that is not restricted to haematopoietic lineages but is preferentially expressed on early haematopoietic cells, T cells, and monocytes. This glycoprotein complex is made of a constant 120,000-140,000 Mr subunit noncovalently associated at the cell surface with subunits of higher Mr ranging from 150,000 to 200,000 on different cell types. Internal labelling with [35S]methionine and pulse-chase experiments revealed that in the cell the 120,000 Mr glycoprotein of this complex is also noncovalently associated with a 100,000 Mr glycoprotein, and that both glycoproteins are independently biosynthesized. This glycoprotein complex is shown by immunoprecipitation by lectin plus antilectin antibodies and by sequential immunoprecipitations to be one of the cell surface structures bound by phytohaemagglutinin on the surface of normal T cells.

Animals↗
PubMed1986

The sheep erythrocyte receptor and both alpha and beta chains of the human T-lymphocyte antigen receptor bind the mitogenic lectin (phytohaemagglutinin) from Phaseolus vulgaris.

We have studied the interaction of mitogenic lectins such as phytohaemagglutinin (PHA) and concanavalin A (Con A) with both surface molecules which, by the use of monoclonal antibodies, are known to trigger T-cell mitogenesis. Monoclonal antibodies recognizing the T-lymphocyte receptor for antigen (Ti) and/or its associated structure, CD3, activate T cells. More recently, a second pathway of activation has been described which involves the sheep erythrocyte binding glycoprotein CD2, a surface molecule distinct from Ti-CD3. Lysates from surface-iodinated T-leukaemia cell lines were treated with lectin and affinity purified anti-lectin antibodies coupled to protein A-Sepharose. We have shown that eluates from Con A/anti-Con A or PHA/anti-PHA immunoprecipitates contained Ti, since a rabbit anti-T alpha serum, which recognizes the native and denatured forms of the constant region of the alpha chain, immunoprecipitated Ti from these eluates. Furthermore, Ti immunoprecipitated by anti-T alpha serum from lysates of surface iodinated E+ lymphocytes was binding to PHA after elution from the immunoprecipitate. When the purified Ti molecule was reduced and alkylated, allowing the permanent dissociation of its alpha and beta subunits, PHA interacted with both chains, whereas anti-T alpha serum immunoprecipitated the alpha chain only. Altogether, these results demonstrate that PHA interacts with both chains of the T cell receptor for antigen on human peripheral T lymphocytes. With the HPB-ALL tumour line, a similar approach showed that both alpha and beta chains of Ti bind to Con A and Ulex europaeus 1 but not Helix pomatia. Affinity chromatography on immobilized lectins and immunoprecipitation with lectin/anti-lectin antibodies were employed to test whether CD2 binds to PHA and Con A. The results show that CD2 from human peripheral T lymphocytes binds both lectins but with a lower affinity for PHA than Con A.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Phenotypic characterization of the thymus microenvironment study of the human thymus architecture.

Phenotypic characterization of the human thymic microenvironment shows the heterogeneity of the epithelial component. Using monoclonal antibody L191, we define here a new antigen common to the flat epithelial cells lining up the thymic capsule and septum, stellate epithelial cells from the subcapsular area and the medulla (M), but lacking on stellate epithelial cells from the inner cortex. Thus, this cell population can be characterized by a series of antigens (TE-4 and P19--shared with HTLV--previously described by B. Haynes et al.) which reflect a common differentiation program--including neuroendocrine specialization--with remarkable differences in the expression of these antigens, occurring during ontogeny and after birth. Another Ab we obtained shows particularities in the cytoskeletal organization of this cell population. Finally the organization of the mesenchymal component was also investigated with a third, anticollagen, antibody. A striking observation we made, using these antibodies, was the relationship between the thymic septum and flat epithelial cells with medullary and Hassal's body (HB) epithelial cells: septae deeply penetrate the medulla so that flat epithelial cells come into direct contact with medullary epithelial cells; in addition, HB are in close contact with the deepest portion of the septae, often separated solely by a single stellate cell. This architectural organization might be related to the differentiation--regeneration process of the thymic epithelium.

Antibodies, Monoclonal↗
PubMed1985

Serological expression after sequential double transfection with purified HLA-A11 gene of mouse fibroblasts carrying human beta-2 microglobulin.

A genomic cosmid library constructed from DNA from a genotyped individual (JF = HLA-A11, Cw-, B38/A26, Cw7, B51) was screened for clones containing class I histocompatibility genes. Among these clones, one was found to carry a 4.8 kb Hind III fragment which is highly correlated with HLA-A11. This clone was used to transfect LMTK+ cultured mouse fibroblast transformants expressing human beta-2 microglobulin. The human beta-2 microglobulin heavy chain-associated determinant was positively detected by the M18 monoclonal antibody. HLA-A11 expression on these doubly transformed cells was specifically demonstrated by complement-dependent cytotoxicity with HLA-A11 + A3-specific but not with HLA-A3-specific monoclonal antibodies. Absorption studies with human alloantisera confirmed the presence on these cells of HLA-A11 determinants and of cross-reacting determinants which absorbed anti-HLA-A1 and -A3 alloantisera. The JF5-J27 transfected cell expressed both heavy and light chains of human class I histocompatibility genes.

Animals↗
PubMed1985

T cell activation via CD2 [T, gp50] molecules: accessory cells are required to trigger T cell activation via CD2-D66 plus CD2-9.6/T11(1) epitopes.

Binding monoclonal antibodies (MAb) both to D66 and 9.6/T11(1) epitopes on the CD2 [T,gp50]-defined molecule produces a high level of T cell mitosis. This was observed with a battery of MAb of different isotypes. In contrast, none of the anti-D66 or anti-9.6/T11(1)Ab could trigger T cell proliferation in combination with anti-T11(3). Moreover, all anti-D66-9.6/T11(1) pairs of MAb tested required monocytes to activate T cells which were recruited through their Fc receptors. Variations among normal individuals were observed in the level of response to anti-D66-9.6/T11(1) pairs of Ab, 75% of a population of French Caucasians giving a high response. The level of response of a given individual was determined by his accessory cells. However, the level of response of an individual appeared to be minimally influenced by the isotype of a peculiar anti-D66 or anti-9.6/T11(1) Ab. The addition of exogeneous IL 2 could overcome the removal of accessory cells or the modulation of CD3 molecules. In contrast, IL 2 receptor appearance was not overcome by removal of monocytes. Thus, T cell activation via CD2 seems to be produced by "touching" several definite regions of this molecule which trigger a cascade of events similar to those produced by mitogenic lectins. One can assume that the appropriate conformational changes of the CD2 molecule induced by anti-D66-9.6/T11(1) pairs of Ab are solely produced when they are presented by accessory cells. This leaves open the question of whether accessory cells would also play a more active role.

Antibodies, Monoclonal↗
PubMed1984

[Differentiation antigens of malignant leukocytes (2)].

One of the most rewarding applications of anti-leucocyte monoclonal antibodies is their use in the study of leukaemias and haematosarcomas. They are now of daily assistance for the diagnosis and classification of these diseases. The availability of malignant cell phenotypes provides a more accurate definition of nosological entities and opens new prospects of a better adaptation of treatment to each individual patient. Moreover, monoclonal antibodies now make it possible to determine the general characteristics of the phenotype of malignant leucocyte populations. Such an improvement in our understanding of these tumours will undoubtedly result in numerous developments during the forthcoming years.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1984

[Human leukocyte differentiation antigens].

Over a small number of years many monoclonal antibodies directed against leucocytes have been produced. Their multiplicity and the various nomenclatures utilized may be disconcerting. As a result of the First International Workshop on Human Leucocyte Differentiation Antigens (Paris, 1982), a very clear correspondence between these different antibodies has been established by regrouping into "differentiation classes", each class corresponding to a given molecular species at leucocyte surface. One of the consequences of this international co-operative study has been the development of a nomenclature system now officially adopted by the World Health Organization. In addition, it is now possible to identify the general characteristics of leucocyte surface molecules, which provides information on their organization and function. The international study is in progress, and the results of the Second Workshop (Boston, 1984) will soon be available.

Antibodies, Monoclonal↗