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Biomedical subjects

L Boumsell

Publications and source records attributed to L Boumsell.

At least 91 records · Page 5Linked to original sources
PubMed1990

Correlation between T cell receptor gamma delta isotypic forms and cytotoxic activity: analysis with human T cell clones and lines.

Three biochemically distinct isotypic forms of the human T cell receptor (TcR) gamma delta structure can be expressed at the cell membrane. This unique variation in structure of TcR, which is due to C gamma gene segments utilization, prompted us to look for isotype-association functional differences. In this regard, we have developed human T cell clones or lines from normal thymus or peripheral blood from several patients. In the present report, we have selected by phenotypic, biochemical, and TcR gene rearrangement analysis representative pairs of IL2-dependent clones or lines for each TcR gamma delta isotypic form. The results showed a lack of correlation between the TcR isotypes and the ability of the cells to proliferate in response to TcR stimulation mediated through the CD3 molecular complexes. By contrast, despite the fact that all of these representative cells exhibit an NK-like activity, as measured by their ability to kill K562, the strongest lytic activity was observed with the cells having the disulfide-bonded form of the receptor. Moreover only those latter cells were able to efficiently kill the LAK-sensitive Daudi cell line.

Clone Cells↗
PubMed1990

K20 and ICO-10 monoclonal antibodies (gp120/200; Thy-1): immunophenotyping of human solid tumours.

Solid tumour cells were shown to express VLA-beta and Thy-1 antigens. For identification of these molecules two monoclonal antibodies, K-20 and ICO-10, characterised in detail previously, were used. Four groups of solid tumours have been identified according to their immunophenotype: VLA-beta+ and Thy-1-; VLA-beta+ and Thy-1+; VLA-beta- and Thy-1+; VLA-beta- and Thy-1-. To a certain extent these groups have been shown to reflect tumour histogenesis: tumours of epithelial origin never expressed an ICO-10+, K20-phenotype while soft tissue sarcomas and neuroblastoma cells never expressed the beta-chain of VLA molecular complexes.

Antibodies, Monoclonal↗
PubMed1990

Utilization of two different T cell receptors by 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 (mAb) reacting either with constant or variable regions of T cell receptors (TcR) alpha beta and gamma delta or with various CD molecules. We analysed a panel of 15 T-ALL and 15 T-LL selected for their cell surface expression of the CD3 molecules. The results indicate that TcR gamma delta is more frequently used than TcR alpha beta in T-ALL (10 out 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 out 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 out of 11 patients) whereas in a unique case V delta 2 gene segment was used. Taken together these results and those indicating that T-ALL cell coexpress the CD1a,b and c molecules strengthen the possibility that even though these leukemic cells express the CD3-TcR complex at their cell surface their normal counterparts are not found in peripheral blood.

Adult↗
PubMed1990

Infiltrating lymphocytes in benign and malignant naevomelanocytic lesions.

Cutaneous melanocytic tumors include benign (naevi) and malignant (melanoma), potentially metastatic lesions. In this report, we show that infiltrating lymphocytes from benign tumors may be expanded in vitro as TIL from melanoma in the presence of autologous tumoral cells and recombinant IL2. Moreover it seems that TIL from primary cutaneous benign or malignant lesions more frequently express the T-cell receptor gamma delta than TIL from metastatic melanoma. Otherwise, a gamma delta + line and a gamma delta + clone extracted from a primary cutaneous melanoma exhibit a specific non MHC-restricted cytotoxic activity against autologous tumor cells. This is the first report of a TCR gamma delta + T lymphocyte cytotoxic activity against a human solid cutaneous tumor.

Cytotoxicity, Immunologic↗
PubMed1989

Analysis of junctional diversity in the preferential V delta 1-J delta 1 rearrangement of fresh T-acute lymphoblastic leukemia cells by in vitro gene amplification and direct sequencing.

To define the junctional diversity of T-cell antigen receptor delta gene rearrangements in fresh T-acute lymphoblastic cells and to correlate cell phenotype with the coding potential of rearrangements, we determined the junctional nucleotide sequences of 13 T-cell antigen receptor delta gene rearrangements involving the preferentially rearranged V (V delta 1) and J (J delta 1) segments using in vitro gene amplification and direct sequencing. We showed that, as in gamma delta+ cell lines, extensive junctional diversity exists in these clones and that this diversity is due both to random nucleotide deletions/additions and to the use of at least two D delta segments. We also showed that a high percentage of these rearrangements are potentially translatable (7:13) and that such functional rearrangements occur in both surface CD3+ and CD3- cells. Comparison of alpha beta versus gamma delta surface expression demonstrates that all CD3+ T acute lymphoblastic leukemias with a functional V delta 1-J delta 1 rearrangement express a surface gamma delta receptor and are recognized by the anti-delta monoclonal antibody delta TCS1, whereas a control CD3+ gamma delta+ leukemic case that had not undergone V delta 1 rearrangement was delta TCS1-. In addition, expression of this monoclonal antibody is not restricted by V gamma or C gamma usage or by the covalent or noncovalent link between gamma and delta chains.

Amino Acid Sequence↗
PubMed1989

A 19-kDa human erythrocyte molecule H19 is involved in rosettes, present on nucleated cells, and required for T cell activation. Comparison of the roles of H19 and LFA-3 molecules in T cell activation.

We have previously described a molecule on the SRBC surface which, in addition to the sheep equivalent of LFA-3, is involved in the process of rosette formation. It is made of a single, 14- to 19-kDa, polypeptide chain, and we termed this molecule S14. We have now identified, on the human E a molecule with a similar Mr albeit somewhat higher (19 kDa). The mAb against H19 efficiently block autologous or homologous rosettes by binding to human E. In addition, purified H19 molecules block rosettes made with human E and SRBC in a dose-dependent manner. The H19 molecule, like LFA-3, is not limited to the E surface, but is also present on many nucleated cells, including T cells and monocytes. Moreover H19, like LFA-3, is required for T cell activation: when we stimulated whole PBMC anti-H19 blocked [H3]TdR incorporation triggered via CD3, but not via CD2, in contrast to anti-LFA-3 that inhibited activation via both pathways. When a mixture of highly purified T-PBL and autologous paraformaldehyde fixed accessory cells (AC) was cultivated, anti-H19 or anti-LFA-3 mAb bound to AC blocked T cell proliferation. When high amounts of rIL-1 (100 U/ml) were added to purified T-PBL, no AC were required to sustain their proliferation upon stimulation via CD2, contrary to stimulation via CD3. When lower amounts of rIL-1 (10 U/ml) were used, fixed AC were still necessary to sustain proliferation via CD2. In this latter situation, anti-H19 mAb bound to AC could no longer inhibit T cell proliferation, whereas the anti-LFA-3 mAb was still inhibitory. When T-PBL were stimulated via CD2 in the presence of 100 U/ml of rIL-1, anti-LFA-3 did not induce any inhibition. Thus the inhibitory effect of anti-H19 and anti-LFA-3 mAb can both be accounted for by an effect on the AC molecules only, and not on the T cell molecules. F(ab')2 fragments of anti-H19 mAb produced the same pattern of inhibition as the whole Ig molecule, excluding an effect via the FcR. Moreover, purified preparations of the H19 molecules also produced inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Cleavage of Langerhans cell surface CD1a molecule by trypsin.

The T-cell surface differentiation antigens expressed on cortical thymocytes are composed of 3 molecules, CD1a (Mr 49,000), CD1b (Mr 45,000), and CD1c (Mr 43,000), which are non-covalently attached to beta 2-microglobulin. In the present study, differences in quantitative binding (immunogold labelling) were observed with four CD1a monoclonal antibodies (mAb), Na1/34, L544, Vit6 and OKT6, on epidermal Langerhans cells obtained through trypsinization and Ficoll-Hypaque sedimentation. These cells were surface-labelled with 125I and then lysed. Immunoprecipitation was carried out with five CD1a mAb, BL6, 10D12.2, L404, L544 and OKT6, and immunoprecipitates were electrophoretically run. All CD1a mAb except OKT6 immunoprecipitated an additional molecule with an apparent relative mass of 27,000, under reducing conditions. CD1a antigen (Mr 49,000) was borne by the same chain of Mr 49,000 on cortical thymocytes and Langerhans cells, whereas the Mr 27,000 molecule was never found on thymic cells. On two-dimensional gel analysis, the Mr 27,000 molecule showed a pattern with 3 major spots with pI of 5.6, 5.9 and 6.2. This Mr 27,000 protein was found to contain one N-linked oligosaccharide residue by endoglycosidase-F treatment. By sequential immunoprecipitation, this Mr 27,000 molecule was shown to be different from the major histocompatibility complex class II beta-chains (DR, DP). As the Mr 27,000 molecule was not precipitated with OKT6, sequential immunoprecipitation confirmed specific recognition of this low molecular weight protein by other CD1a mAb. The protein of apparent molecular mass 27,000 was considered to be a breakdown product of Mr 49,000 (CD1a) antigen. These results suggested that the CD1a molecule was sensitive to trypsin.

Antibodies, Monoclonal↗
PubMed1989

A surface glycoprotein complex related to the adhesive receptors of the VLA family, shared by epidermal Langerhans cells and basal keratinocytes.

A murine monoclonal antibody, designated K20, was raised by immunization with a human malignant T-cell line. It reacted specifically with membrane glycoprotein complexes on early haematopoietic cells, T cells, and monocytes. In epidermis, K20 specifically reacted with Langerhans cells and basal keratinocytes, as demonstrated by double labeling experiments. Membrane immunoprecipitation analysis demonstrated that the antigen identified by K20 on lymphoid cells and epidermal cells was different. While on lymphoid cells, K20 recognized glycoprotein complexes made of a constant 130-kD subunit associated with subunits of higher molecular weight ranging from 150 to 200 kD, a complex of 105-145 kD was precipitated from Langerhans and basal cells. Metabolic labeling studies demonstrated that these proteins were synthesized by the basal cells. The antigen identified by K20 was thought to belong to the integrins, a family of cell surface receptors that play a role in cell adhesion, cell interactions, wound healing, and immune defense mechanisms. K20 is the first monoclonal antibody that specifically recognizes a membrane antigen common to Langerhans and basal cells. Additionally, K20 is the first of five reported monoclonal antibodies to have been characterized on the epidermal cells that detect antigens shared by lymphoid subpopulations and normal basal keratinocytes.

Antibodies, Monoclonal↗
PubMed1989

CD1 expression on B-CLL lymphocytes.

In a previous report we showed that D47 CD1a monoclonal antibody positively labelled B-CLL cells of some patients. Six cases were selected to further characterize CD1 antigenic expression at the leukaemic cell surface using flow cytometry with a battery of six CD1a, two CD1b and two CD1c monoclonal antibodies. CLL cells were positively labelled with CD1a antibodies except OKT6 and NA1/34; in all cases they were CD1b negative and CD1c positive. These results suggested that CD1a, c epitopes can be detected on leukaemic B cells in addition to other T cell differentiation antigens. In view of recently published data demonstrating the presence of CD1c molecule in normal B cell subsets, our results further question the relationship of B-CLL with a restricted subpopulation of B cells.

Antibodies, Monoclonal↗
PubMed1989

[ICO-35 monoclonal antibodies to the antigen of acute lymphoblastic leukemia].

ICO-35 monoclonal antibodies (Mabs) were produced following BALB/c mouse immunization with peripheral blood cells from a patient with lymphoid type of chronic myeloid leukemia in blast crisis (SML BC) ICO-35. Mabs detect antigen on CD10-positive cells from patients with acute lymphoblastic leukemia, CML BC, CD10-positive cells of Reh line and are not bound to other cells. Comparative studies of reactivity of ICO-35 and K 503 Mabs to CD10 antigen revealed their similarity. However, in contrast to K503 ICO-35 Mabs do not react with granulocytes.

Animals↗
PubMed1989

Immunologic analysis of a thousand cases of acute leukemia. French Groupe d'Etude Immunologique des Leucémies (GEIL).

The French Groupe d'Etude Immunologique des Leucémies (GEIL), now in its fifth year of existence, has collected extensive immunological information on more than 1,000 leukemia patients. The rationale of such multicentric group is to improve immuno-phenotyping and investigate rare phenotypes, with relevance to the clinical outcome of the patients. These aims are described and exemplified through 3 of the first studies performed.

Antigens, Differentiation↗
PubMed1988

A T cell surface molecule different from CD2 is involved in spontaneous rosette formation with erythrocytes.

Increasing evidence indicates that rosettes which spontaneously from between human T cells and E might be of physiologic relevance. We show here that another T cell-surface molecule than CD2 is involved in rosette formation. Four mAb have been obtained reacting with human T cells that block rosettes with E from many species, including autologous cells. They react with a molecule, we termed E2, which is actively synthetized by T and monocytic cells. Immunoprecipitation revealed a major 32-kDa band. Immunoblots revealed a major 32-kDa band and a minor 20-kDa band. This molecule was detected on all T cells tested--and present at high densities on corticothymocytes, but at low densities on medullary thymocytes. It was also found on monocytes but not on B cells. However B-CLL cells did carry this molecule. E2 molecules were also detected on nonhematologic cells. Together with the recent evidence that 3 molecules from the erythrocyte surface are also involved for rosettes, intricate molecular interactions would account for adhesion of T cells to autologous E and possibly autologous nucleated cells.

Antibodies, Monoclonal↗
PubMed1988

The required interaction between monocytes and peripheral blood T lymphocytes (T-PBL) upon activation via CD2 or CD3. Role of HLA class I molecules from accessory cells and the differential response of T-PBL subsets.

Previously, we have shown that paraformaldehyde-fixed monocytes are able to fully complement, in terms of [3H]dThd incorporation, a primary stimulus delivered to purified T cells by monoclonal antibodies (mAb) reacting with CD3 or CD2 molecules. Here, we show that depending on the stimulus used (CD3 mAb or different pairs of CD2 mAb) HLA class I molecules from monocytes are directly involved in complementary signals provided to T cells. This was evidenced by the following observations: (a) mAb reacting with the heavy or light chain of class I molecules, or their Fab fragments, completely blocked proliferation of peripheral blood lymphocytes (PBL) activated by CD3 mAb; (b) mAb against the heavy chain of HLA class I but not against beta 2-microglobulin partially blocked (approximately equal to 50%) PBL activation by the CD2 "GT2 + T111" mAb pair but did not block activation by CD2 "D66 + T111" mAb; (c) this pattern of inhibition was observed when anti-class I mAb were used in the soluble phase or when they were bound to monocytes subsequently fixed with paraformaldehyde and cultivated with purified autologous T cells; (d) fixed monocytes are able to restore interleukin (IL) 2 receptor expression on purified T cells stimulated by CD3 mAb or CD2 "GT2 + T111", contrary to anti-HLA class I mAb-pretreated monocytes. The inhibitory effects of anti-HLA class I mAb bound to monocytes were not found to be reversed by recombinant IL2 or recombinant IL1. We assume that HLA class I would be involved in two or more signals delivered to T cells by monocytes, the requirement in those signals depending on the initial stimulus applied to T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

Intermolecular complexes between three human CD1 molecules on normal thymus cells.

The first cluster of differentiation (CD1) defines at least three distinct human thymic cell-surface differentiation antigens-CD1a, CD1b, and CD1c. We looked for structural homology of the three CD1 heavy chains at their peptide level by two-dimensional peptide maps. We show here that the CD1a Mr 49,000 heavy chain and the CD1b Mr 45,000 heavy chain appear to be more homologous to each other than to the CD1c Mr 43,000 heavy chain and that only one tyrosil peptide is common to the three heavy chains. Study of the CD1 heavy chains from several individuals reveals a very limited polymorphism of these molecules. We also demonstrate here that CD1a or CD1a-like molecules and other CD1 molecules can form intermolecular complexes on the surface of normal thymus cells. Molecules that are structurally very similar to CD1a molecules are associated noncovalently either with CD1c molecules or with CD1b molecules, and only CD1a molecules can associate covalently with CD8 molecules. In contrast, we could not find these intermolecular complexes on the surface of leukemic T-cell lines in culture.

Antibodies, Monoclonal↗
PubMed1988

Comparison of signals delivered through CD3 and CD2 for T-cell activation: the role of calcium influx and interleukin 1.

In the absence of monocytes, resting T lymphocytes extensively purified from human peripheral blood failed to proliferate when stimulated with a mixture of calcium ionophore, which elevates intracellular calcium levels, and TPA, which activated protein kinase C. A third signal, i.e., the triggering via CD3 or CD2 molecules, was necessary in order to observe proliferation. These highly purified T cells required the presence of monocytes in both CD3 and CD2 systems for their proliferation. Exogenous interleukin 1 clearly substituted for monocytes in CD2- but not in CD3- triggered T-cell proliferation. In contrast, the effect of CD2 and CD3 antibodies on Ca++ influx was apparently not dependent on the presence of monocytes. In the presence or absence of the monocytes, CD3, as well as certain combinations of CD2 monoclonal antibodies including the D66 monoclonal antibody, were able to increase the intracellular calcium concentration as measured by Quin 2 fluorescence. EGTA, a Ca++ chelator, completely inhibited CD2- and CD3- mediated T-cell proliferation, indicating that calcium uptake is necessary during the T-cell proliferation. The addition of TPA abrogated the inhibitory effect of EGTA and completely restored the response of the T cells stimulated by CD3, but not by CD2, monoclonal antibodies. In the CD2 pathway, EGTA-inhibited proliferation of T cells could be completely restored by addition of exogenous interleukin 2 as well as exogenous recombinant interleukin 1. Our results indicate that EGTA inhibits the production of interleukin 1 but has no direct effect on either interleukin 2 production or on Tac antigen expression. In this system, recombinant interleukin 1 alpha demonstrated a more potent ability for restoring the T-cell response than did recombinant interleukin 1 beta. These results suggest that interleukin 1 could act as a potent costimulatory factor in the non-antigen-specific T-cell activation.

Antibodies, Monoclonal↗
PubMed1988

HLA class I molecules are associated with CD1a heavy chains on normal human thymus cells.

The molecules encoded by the major histocompatibility complex play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. The function of the CD1 molecules, which are homologous to the major histocompatibility complex-encoded molecules but are encoded on human chromosome 1, is not known. HLA class I molecules and CD1a heavy chains share the ability to associate with several different cell-surface molecules. We show here, by several technical approaches, that HLA class I molecules are associated with CD1a heavy chains on the surface of normal thymus cells. The functional significance of this association during T-cell differentiation is discussed.

Antibodies, Monoclonal↗
PubMed1988

CD1 expression in B-CLL cells.

The peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or not clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs were chosen since they detected B or CD1-8 T cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B cell antigens recognized by BL14, Y2955 and anti-class II moAbs were constantly expressed in leukemic cells, while B-cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T cell markers including several epitopes of the CD1 group were also found to be present on the leukemic cell surface in several cases. To further extend these data, 6 cases were selected for labelling with a battery of 6 CD1a, 2 CD1b and 1 CD1c moAbs. These results suggested that CD1a,c epitopes can be detected on leukemic B cells in addition to other T cell differentiation antigens.

Antibodies, Monoclonal↗