Biomedical subjects

P Debre

Publications and source records attributed to P Debre.

At least 73 records · Page 4Linked to original sources

PubMed1989

HLA linked immune response to S and pre-S2 gene products in hepatitis B vaccination.

In order to detect a possible HLA linked genetic control of human immune responses to hepatitis B virus, forty healthy adult persons of the same age typed for HLA-A, -B and -DR antigens, were vaccinated against virus hepatitis B and sequentially tested for anti-HBs and anti-pre-S2 antibodies. They received three injections of Hevac-B Pasteur vaccine, the second 1 month and the third 3 months after the first. Following the third immunization, 38 individuals (95%) had a protective level of anti-HBs antibodies and 17 (42.3%) had a positive level of anti-pre-S2 antibodies. HLA-A11 antigen was significantly more frequent (pc = 0.007) among anti-HBs high responders than low responders. In addition, anti-HBs high responders were more frequently HLA-DR1, and less frequently HLA-DR4 and DR7 positive; corrected values, however, were not significant. Anti-pre-S2 high responders showed an apparent increase of HLA-B7, B14 or DR3 antigens, when compared to low responders (pc not significant).

Adult↗

PubMed1989

T cell receptor gamma/delta+ lymphocyte subsets during HIV infection.

The gamma/delta T cell receptor is expressed on 1-15% of normal human peripheral blood lymphocytes (PBL). This subpopulation is recognized by anti-TcR-delta 1 MoAb which is functionally defined as a pan-delta MoAb. Two other antibodies, anti-Ti-gamma A and anti-delta-TcS1 are directed at variable determinants of either the gamma or the delta chain, respectively. In normal individuals anti-Ti-gamma A characterizes two thirds of the TcR-delta 1+ subpopulation whereas anti-delta TcS1 reacts with most of the delta-TcR1+, Ti-gamma A- cells. In the present study, we have used these three MoAbs to characterize the TcR gamma/delta+ peripheral lymphocytes during HIV infection. Fifty patients at three distinct clinical stages (SPC/PGL, ARC, AIDS) of the infection have been studied. The Ti-gamma A+ subset in the whole group accounted for 3.45% of PBL and did not differ from controls; it was also unchanged when the three groups were analysed separately. The Ti-gamma A+ circulating cells were in a resting state as assessed by the absence of surface-expressed activation markers. In contrast, in some patients the proportion of circulating TcR-delta 1+, Ti-gamma A-, delta TcS1+ cells was increased (4.75%) leading to an inversion of the Ti-gamma A/delta-TcS1 ratio. Altogether, those data suggest a conservation of the Ti-gamma A+ subset during HIV infection, contrasting with an increase of the delta-TcS1+, Ti-gamma A- fraction in some cases.

AIDS-Related Complex↗

PubMed1989

T-cell nonmalignant clonal proliferation in ataxia telangiectasia: a cytological, immunological, and molecular characterization.

Cytogenetically abnormal T-cell nonmalignant clones are a characteristic feature of ataxia telangiectasia (AT). Here, we study a t(14;14) clone from a patient with AT, and provide a cytological, immunological, and molecular characterization. This cellular population is clonal at the molecular level, but is phenotypically heterogeneous, with CD4+CD8+ and CD4-CD8+ cells. Although these cells do not divide in the peripheral blood, a majority of them are found in G1 phase and express the membrane antigen 4F2, a very early marker of activation. Many similarities are found between this nonmalignant AT clone and T-cell prolymphocytic leukemia at the morphologic, cytogenetic, and immunologic levels, despite the different clinical courses associated with these proliferations. We hypothesize that the t(14;14) translocation is linked to the abnormal morphology and immunophenotype of the AT clone cells, but that this translocation confers only a preactivated state to the cells. A complete malignant transformation would then be due to secondary events.

Adolescent↗

PubMed1988

PGE2-induced cyclic AMP accumulation in human CD4+ T cells is strongly enhanced during the CD2-mediated activatory process.

The effect of a mitogenic combination of two different anti-CD2 monoclonal antibodies on the PGE2-stimulated and basal cAMP production in human CD4+ T cell clones was investigated. The anti-CD2 stimulation strongly potentiates the PGE2-induced cAMP production while both PMA and A23187 produced a less potent effect. On the opposite the anti-CD2 treatment is without any effect on the basal cAMP level contrasting with a marked increase of intracellular cAMP concentrations with A23187 or the combination of A23187 and PMA. These results suggest that activation of CD4+ human T cells via the CD2 molecule significantly influences the cAMP-related transduction pathway. Although PMA and A23187 also modulate the activity of this pathway, their effect in this model is more likely mediated through an amplification of basal cAMP production.

Antibodies, Monoclonal↗

PubMed1988

Positive effects of interferon-alpha on B cell-type chronic lymphocytic leukemia proliferative response.

We studied the effect of recombinant interferon-alpha (IFN-alpha) on the proliferative response of normal human B cells and of lymphocytes from 10 patients with B cell-type chronic lymphocytic leukemia. We show that IFN-alpha, which has no effect on B cell proliferation when used alone, can synergize with anti-mu antibody and can support DNA synthesis by anti-mu activated B cells. This was observed with normal B cells and in 4 of 10 patients with B cell-type chronic lymphocytic leukemia. These four patients were all responders to B cell growth factor (BCGF), whereas the responsiveness to IFN-alpha was not correlated with that of IL-2. The positive functional relationship between IFN-alpha and BCGF in these patients is emphasized by the synergistic effect of these two factors in two of these patients, and the lack of inhibition of BCGF response by even supraoptimal concentrations of IFN-alpha. Among the subgroup of patients unable to respond to IFN-alpha, a synergy between IFN-alpha and IL-2 could be observed.

Adult↗

PubMed1988

Evidence for expression of two distinct T cell receptor beta-chain transcripts in a human diphtheria toxoid-specific T cell clone.

We have cloned and sequenced the human T cell receptor alpha- and beta-chains cDNA present in a lambda gt10 library derived from a human CD4+ diphtheria toxoid-specific T cell clone, PH28. Two 1.3-kb beta-transcripts within frame V, D, J joining were found. These two functional beta-transcripts use two members of different V beta-families, V beta 3 and V beta 4, one joined to D beta 1-1, J beta 1-1, C beta 1, the other joined to D beta 1-1, J beta 2-1, C beta 2. Moreover, we have cloned the two different V beta germ-line counterparts whose sequences confirm that these two V beta are not pseudogenes. Analysis of T cell receptor beta and alpha rearrangements in PH28 showed that a single rearrangement on each chromosome could be assigned either at the J beta or the J gamma loci. These results strongly suggest an absence of allelic exclusion for 1.3-kb mRNA beta-transcripts in a human antigen-specific T cell clone.

Amino Acid Sequence↗

PubMed1988

Conjunctival biopsy in Sjögren's syndrome: correlations between histological and immunohistochemical features.

We have examined conjunctival biopsies from nine primary and two secondary cases of Sjögren's syndrome. In all cases histopathological examination revealed metaplasia of the conjunctival epithelium associated with a reduced number of goblet cells and a polymorphic inflammatory cell infiltrate of the stroma. Using monoclonal antibodies with texture analysis of stained preparations we have shown that in all cases the lymphocytic infiltrate was predominantly T-cell but with substantial numbers of IgA and IgG secretory B-cells in three cases. The number of Langerhans cells present was reduced in biopsies showing the most marked degree of epithelial metaplasia.

Adult↗

PubMed1988

Phenotypic heterogeneity of B- and T-cell differentiation antigens in B-CLL.

Peripheral blood from 38 B-CLL patients was studied by flow cytometry with 25 clustered or non-clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs chosen 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. The relationship between the various clinical and/or biological features of the disease and the cell surface phenotype was studied. Our results indicated a correlation between the lymphoid cell reactivity with M241 (CD1) and BL13 (CD21) and the severity of the disease.

Antibodies, Monoclonal↗

PubMed1988

Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Synergistic effect of recombinant IL 2 and interferon-gamma on the proliferation of human monoclonal lymphocytes.

We studied the effect of interferon-gamma (IFN-gamma) on the proliferation of lymphocytes from 10 B-type chronic lymphocytic leukemia (B-CLL) patients. In no instance did IFN-gamma induce a proliferative response whether used alone or in combination with anti-mu antibody (Ab). This was observed regardless of the responsiveness of a given patient's cells to interleukin 2 (IL 2) and to B cell growth factor (BCGF). In contrast IFN-gamma strongly and reproducibly synergized with IL 2 (but not with BCGF) to support B-CLL proliferation in five of the 10 patients. The effect of IFN-gamma was dose related and could be inhibited by an anti-IFN-gamma monoclonal Ab. A monoclonal Ab toward the IL 2 receptor molecule was also inhibitory. Preincubation with IFN-gamma potentiated the responsiveness of B-CLL to IL 2 in secondary cultures, showing that IFN-gamma exerts its effect before that of IL 2.

B-Lymphocytes↗

PubMed1987

Monoclonal B-cell response to diphtheria toxoid: evidence for cross-reactive epitopes.

Our previous studies on the human specific B- and T-cell responses against diphtheria toxoid (DT) had shown that the B- and T-cell antigenic determinants were mostly assembled topographic sites with large intra-molecular cross-reactivities. In order to characterize further the B-cell responses against DT, and to investigate these cross-reactivities, we have produced 54 murine monoclonal antibodies (moAbs) against the native DT. Determination of their antigenic specificity showed that 25 moAbs recognized conformational determinants on the native DT, 20 moAbs reacted against the A fragment (DTA) of the toxin, and nine moAbs reacted with at least three distinct highly purified CNBr peptides of the B fragment (DTB); some of them simultaneously recognized two or three purified CNBr peptides of DTB. As shown by cross-inhibition studies, the epitopes cross-reacting with those moAbs were distinct. Previously described sequence data indicated that these epitopes were not induced by repetitive amino-acid sequences. Finally, a cross-reactive idiotype was shared by moAbs specific for the CB1 and the CB3 peptides of DTB. Altogether, these data indicate that anti-DT moAbs are mostly directed against conformational determinants, and may cross-react with several DTB CNBr peptides.

Animals↗

PubMed1987

Functional effects of monoclonal antibodies (mAbs) against human polymorphonuclear (PMN) adherence antigens.

Two mouse monoclonal antibodies (mABs), 25.31 raised against an subunit epitope of LFA1 antigen and Mol against an epitope of the complement receptor type 3 (CR3) were used for investigating their effects on human polymorphonuclear (PMN) functions. The two mABs have an inhibitory effect on PMN adherence. Furthermore, the PMN adherence strength depends upon the support and the adherence induces the capping process of these antigens. Other PMN functions dependent upon adherence were also altered by these two mAbs: random locomotion and that directed by formyl-methionyl-leucyl-phenylalanine (FMLP) or by activated serum, degranulation induced by opsonized or non opsonized zymosan but not by phorbol myristate acetate (PMA), iodination, K562 cell cytotoxicity. Luminol enhanced chemiluminescence of PMN was diminished by both mAbs when PMN were stimulated either by opsonized zymosan or by PMA. Our results confirm other workers' findings, and they are consistent with PMN functional abnormalities observed in children with congenital LFA1, Mol antigens defect.

Antibodies, Monoclonal↗

PubMed1987

Comparison of blocking effects of monoclonal antibodies anti-MO1-alpha and anti-LFA1-alpha on human neutrophil functions.

In order to analyse the role of LFA1 and MO1 on neutrophil functions, the blocking effects of two monoclonal antibodies (MAb), one (anti-MO1) recognizing an epitope of the MO1-alpha chain and the other (25.31) an epitope of the LFA1-alpha chain, were measured. Adherence of 51Cr-labelled control neutrophils was 66 + 8% (mean +/- 1 SD) on plastic nuclon plates; this figure decreased to 33 +/- 5% and 23 +/- 6% of control adherence when the neutrophils had been pretreated with anti-LFA1-alpha (anti-alpha L) and anti-MO1-alpha (anti-alpha M), respectively. On another support (plastic culture chambers), 84 +/- 6% of control neutrophils adhered and the adherence of neutrophils pretreated with anti-alpha L or anti-alpha M was 10% and 43% of the control figure, respectively. These results show that adherence of neutrophils is dependent upon the plastic used. Moreover, inhibition of adhesion by the two MAbs was also dependent upon the support used for the assay, suggesting that MO1 and LFA1 may be surface proteins with different specificities. Both antigens capped upon adhesion, while they were randomly distributed in resting neutrophils. Anti-alpha L inhibited (congruent to 50%) locomotion more than did anti-alpha M (congruent to 25%), without altering chemoattractant-induced shape changes. These results suggest that the two MAbs inhibit chemokinesis but not chemotaxis. Many other adherence-associated functions, such as ingestion of opsonized Klebsiella pneumoniae, and cytotoxicity towards K/562 cells were decreased more by anti-alpha L than by anti-alpha M. In contrast, chemiluminescence and iodination induced by opsonized zymosan were inhibited more by anti-alpha M than by anti-alpha L. Degranulation induced by zymosan or opsonized zymosan was altered by anti-alpha M only, and this alteration involved azurophilic and not specific granules. Chemiluminescence induced by phorbol myristate acetate was inhibited to a greater extent by anti-alpha M than by anti-alpha L, while degranulation induced by phorbol myristate acetate was not altered by either of the two Mabs.

Adult↗

PubMed1987

Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal.

We studied the effects of B cell directed growth factors on B lymphocytes from 11 patients with chronic lymphocytic leukemia (B-CLL). B-CLL lymphocytes were costimulated with anti-mu antibody (Ab) and with three growth factor preparations: recombinant IL2, B cell growth factor (BCGF) (20 kiloDalton (kD) BCGF) and a high molecular weight BCGF (50 kD BCGF). IL2 was the more active factor (in six of 11 patients). The effect of IL2 was dependent on a costimulation with anti-mu Ab or occurred independently of anti-mu Ab, according to the patients. This pattern of reactivity did not correlate with the presence or absence of the IL2 receptor (IL2-R) molecule on fresh B-CLL lymphocytes. Five patients responded to the 20 kD BCGF. Although four of them were also strong responders to IL2, one strongly responded to the 20 kD BCGF and did not respond to IL2. Only one patient responded to the 50 kD BCGF. When an anti-IL2-R Ab was introduced into the culture, only the responsiveness to IL2 was abolished: thus both 20 kD and 50 kD BCGFs activate B-CLL lymphocytes independently of the IL2-R. These results show that several B cell directed growth factors can act independently to support the proliferation of B-CLL lymphocytes.

Antigens, Surface↗

PubMed1986

Sequences and diversity of human T cell receptor beta chain variable region genes.

The nucleotide sequences of 22 human T cell antigen receptor (TcR) beta chain variable region genes isolated from various T lymphocytes have been analyzed. Of the 19 variable gene segment (V beta)-containing sequences, 17 were unique. The V beta gene segments were grouped into 11 families. Comparisons were made with the data of Concannon et al. to unify the nomenclature. The data is consistent with a total V beta gene segment repertoire with a most probable value of 38 members and an upper bound of 104 members at the 95% confidence level. Southern blot data of germline DNA using selected TcR V beta cDNAs as probes support this estimate. The human repertoire is approximately three to four times greater than that reported for the mouse. Explanations for this discrepancy are proposed.

Base Sequence↗

PubMed1986

Expression of MHC class II and Tac antigens on IL2-activated human T cell clones that can stimulate in MLR, AMLR, PLT and can present antigen.

The expression of interleukin 2 (IL2) receptor and HLA-DR, DQ, and DP antigens on the surface of four diphtheria toxoïd (DT)-specific T lymphocyte clones (TLC) and two TLC specific for an allogeneic EBV-transformed cell line was investigated with the use of monoclonal antibodies (MoAbs) that recognize defined molecules or epitopes. Incubation of a resting TLC with IL2 resulted in a 10- to 30-fold increase in the level of DR, DQ, and Tac antigen expression. On the other hand, incubation of an activated TLC with IL2 decreased for 1 to 6 hr the level of expression of these three antigens. Anti-FA MoAbs did not react with any of the TLC tested suggesting that the expression of DR, DQ, and DP antigens is dissociated on activated TLC. Surface-marker analysis with anti-DR MoAbs indicated that DR epitopes were differently expressed at some activation stages of the TLC. Functional studies showed that activated TLC can stimulate in MLR, AMLR, and PLT. These proliferative responses were inhibited by preincubating the TLC with anti-DR MoAbs suggesting that the stimulatory determinants were predominantly DR molecules. In addition, some TLC can act as antigen presenting cells in DT-specific proliferative responses. These results indicate that MHC class II molecules on activated T lymphocytes may be relevant for the control of specific immunologic responses in vivo.

Antibodies, Monoclonal↗

PubMed1986

CD 1-8 antigens on human diphtheria toxoid T lymphocyte clones: expression and modulation by TPA, sodium butyrate, and 5-azacytidine.

The modulation of antigen expression on the surface of TLC by different differentiation inducers as well as the inhibition of the TLC proliferative response by specific MoAbs may lead to a clarification of the role of various surface molecules studied in antigen-specific T-cell response. We investigated the expression of CD 1-8 antigens on the surface of diphtheria toxoid or varidase specific TLC with a series of MoAb. CD1 and CD8 antigens were not expressed on the proliferative TLC. CD2, CD3, CD4, and CD5 antigens were homogeneously expressed on all TLC in contrast to CD6 and CD7 antigens which were present on only a fraction of the cells in a given TLC. In functional assays, anti-CD2, anti-DR VI-15C, and anti-CD25 MoAbs blocked the proliferative response to DT and anti-CD3, anti-CD4, anti-D44 MoAbs had intermediate inhibition effects. Anti-CD5, anti-CD6, and anti-CD7 MoAbs did not inhibit the proliferative response. Surface marker analysis revealed that the expression of CD2 to CD7 antigens (and also CD25) may be modified following incubation of the TLC with TPA or sodium butyrate but not with 5-azacytidine. TPA greatly decreased the expression of CD3 and CD4 antigens after a 6-hr exposure. Preincubation of TLC cells with TPA inhibited the mitogenic effect of anti-CD3 MoAbs on TLC cells in proliferative assays, but did not inhibit their capacity to proliferate in response to DT despite low levels of CD3 and CD4.

Antibodies, Monoclonal↗

PubMed1985

T-lymphocyte progenitors in man: phenotypic characterization of blood and bone marrow T-colony forming cells.

Human T-lymphocyte cell precursors are driven to proliferate in vitro and to form T-cell colonies during incubation with a PHA-stimulated lymphocyte supernatant (P-SUP). By using cell affinity chromatography, we selected different populations of putative T-lymphocyte precursors in the blood and bone marrow. T-colony forming cells (T-CFC) were found in each of these different populations of cells with phenotypically immature cell surface markers: OKT11- cells or OKT4-/OKT8- cells in the blood and bone marrow, and OKT10+ or RFB-1+ cells in the bone marrow. Pretreatment with OKT3, together with a monoclonal anti-DR antibody and complement, did not abrogate the T-colony forming capacity. The OKT4-/OKT8- precursors were more radiosensitive (Do = 105 rads) than OKT4+, OKT8+ cells (Do = 360 rads) in their T-colony forming capacity. These results suggest that T-CFC could be induced to grow in agar from cells populations representing early steps of the T-cell lineage.

Aged↗