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Biomedical subjects

V Lepage

Publications and source records attributed to V Lepage.

At least 73 records · Page 4Linked to original sources
PubMed1985

Evidence for a new HLA class II determinant present on cells from HLA-DR1 and/or -DR4 individuals.

Evidence for a new HLA class II specificity is presented. It is recognized by LE serum, which reacts with most DR1 and/or DR4 individuals (r = 0.86). Its frequency in the French population is 0.33. Absorption-elution experiments showed that the serum reactivity was not due to a mixture of anti-DR1 and anti-DR4 antibodies, but to a single antibody population which could be absorbed on and eluted from both DR1(+) or DR4(+) cells. LE specificity seemed to be expressed on DR but not on DQ molecules since the serum reacted with and could be absorbed by DR+,DQw- cells; it did not react with a DR-,DQw+ mutant cell, but did react with the DR+,DQw+ parental cell. The relationship between LE specificity and MC1 and Te23 specificities remains to be determined.

Adult↗
PubMed1985

Study of HLA antigens of the Martinican population.

This is the first time a study has been undertaken on the HLA profile of the Martinican population, a population which is essentially the product of intermixture between African-Negroes and French Caucasians. Two hundred and thirty-eight nonrelated subjects were typed for the A and B loci, 158 subjects for C locus and 128 for DR locus. After analysis of our parameters (antigen and gene frequencies, linkage disequilibria, etc.) and their comparison to those found in the Black and Caucasian control populations, we came to the conclusion that our racially-mixed population is closer to the African-Negro population than to the French Caucasian. A study of the average gene flow enabled us to evaluate the Caucasian contribution as being about 30%. This figure is subject to change inasmuch as racial intermixture continues. Socio-cultural variables are assumed to play a minimal role, given the high rate of illegitimacy.

Africa↗
PubMed1985

[HLA and myasthenia. Subdivision in 3 categories].

Genetic susceptibility (HLA types), clinical and pathological findings, amount of acetylcholine receptor antibodies and T lymphocyte subpopulations were studied in 63 patients with Myasthenia Gravis (MG). The frequency of HLA-DR5 was increased among patients (0.50 versus 0.23 in controls, pc less than 0.01, relative risk 3.3) and that of HLA-DR3 previously described as associated with MG was slightly increased (0.31 versus 0.20 in controls). The relative frequencies of two T cell subpopulations (T4 helper and T8 suppressor/cytotoxic lymphocytes) were normal in HLA-DR5 positive patients while the ratio T4/T8 was increased in other MG patients, who were HLA-DR3 (p less than 0.005). The high rate was due to an increase in the absolute number of T4 lymphocytes (p less than 0.001). HLA-DR3 patients were mostly women with early onset of a severe form of the disease, marked by the presence of thymic follicular lymphoid hyperplasia. A third genetic susceptibility to this disease was recently described in patients treated with D-penicillamine, the antigenic frequency of HLA-Bw35, DR1 is significantly increased. These 3 types of association between HLA and myasthenia gravis can be related to three different physiopathological mechanisms: the first two are probably linked to individual immunity (inductor/suppressor disequilibrium), in the third association, the mechanism is immunopharmacological.

Adult↗
PubMed1984

Influenza A hemagglutinin-specific T cell clones strictly restricted by HLA-DR1 or HLA-DR7 molecules.

The antigenic specificities, major histocompatibility complex restrictions and functional properties of influenza virus-specific proliferative cloned cell lines have been studied. These lines were specific for the H3 hemagglutinin subtype of influenza A viruses. By using a large panel of HLA-phenotyped antigen-presenting cells, it was found that the polymorphic structures, defined as DR1 and DR7 molecules, or closely associated structures, function as the restricting elements. We excluded for these lines a possible restricting role of supertypic specificities, known cross-reacting elements on DR molecules, or products of other loci in known linkage disequilibrium with the HLA-DR molecules. Such exquisitely restricted clones might be of great help in the class II typing of antigen-presenting cells. Their specific activity was stable for several months. This has allowed the study of some functional properties of these long-term-cultured cloned cell lines: interleukin 2 sensitivity and production, helper function in specific antibody synthesis and ability to stimulate in mixed leukocyte reactions.

Adult↗
PubMed1984

Non HLA antigenic determinants expressed on activated T and B human lymphocytes.

Human antigenic determinants present on activated T and B lymphocytes and not on resting B and T cells defined by serological studies are reported. The reactivity of 13 sera against human PBM activated by various agents was tested using microlymphocytotoxicity technique. Results showed that generally similar reactions are present on B and T blasts whatever the technique of activation (PHA, ConA, PWM, TCGF, EBV and allo activation). Absorption elution studies with 5 sera on 10 alloactivated cells clearly demonstrated their independence from DR determinants. The analysis of results obtained by these 15 sera on blasts from 50 donors showed no correlation with HLA-A, -B, -C, DR and -MB antigens, neither can it be HT (Qa-like) antigens. Furthermore, 5 clusters of sera are reported. The weak correlation coefficients cannot affirm the existence of a system with an allelic distribution although each cell except one out of a panel of 50 individuals carries at most 2 specificities. The segregation of 3 of these specificities within 5 informative families showed no linkage with HLA genes.

B-Lymphocytes↗
PubMed1981

Alloantigens expressed on activated human T cells different from HLA-A, B, C, and DR antigens.

This study investigates alloantisera containing antibodies directed against antigens which are expressed on alloactivated human T lymphocytes but are absent on resting T and B cells. Among 39 defined anti-HLA-DR sera from multiparous women we found six sera giving positive reactions (more than 25 percent cytotoxicity) on in vitro alloactivated T cells, though negative reactions with resting B or T cells from the donors of either the responding or stimulating cell populations used for alloactivation. Two such sera were submitted to absorption and elution studies. Absorption of these sera with activated T cells did not remove the anti-HLA-DR activity. Furthermore, the antibodies eluted from activated T cells did not react with B cells but were positive only on activated T cells. In addition, we absorbed the sera with B cells and observed that they remained positive on activated T cells. The positive reactions do not seem to be due to either the passive acquisition of antigens from the stimulating population or to low levels of HLA-specific antibodies. As one of the sera we studied intensively gave clear positive and negative reactions on a panel of activated T lymphocytes, we believe it may recognize an antigen of an allogeneic system expressed on alloactivated human T cells.

Antibody Specificity↗
PubMed1981

Regulation of the human allogeneic proliferative response in vitro.

We have investigated the glass-wool-adherent characteristics of human lymphocytes able to suppress allogeneic proliferation in vitro. We observed that: (1) Suppressor cells obtained after in vitro priming and their precursors are adherent to glass wool, whereas cytotoxic cells and their precursors are not; (2) primed cells adherent to glass wool are mainly HLA-DR positive, while nonadherent cells are HLA-DR negative or weakly positive; (3) the nonadherent, unprimed T cells used as responder cells in a primary MLR are more readily suppressed by suppressor cells than the same cells unfiltered. This may suggest an enrichment of 'acceptor' cells for suppression.

Cytotoxicity, Immunologic↗
PubMed1981

Screening and use of high titered anti-HLA-DR sera in PHA-blast complement fixation and B-lymphocytotoxicity techniques.

Screening for anti-HLA-DR sera was performed by complement fixation on PHA stimulated peripheral blood lymphocytes (PHA-CF), or cultured B lymphoid cell lines. Out of 1,350 sera from multiparous women, multitransfused patients, and patients transfused during extra-corporal circulation (ECC), 219 contained anti-HLA-DR activity (16.2%). Anti-HLA-DR antibodies developed after ECC were often high titered (1:10 to 1:100). In half of these sera anti-HLA-A, B antibodies were weak or absent, making it possible to use then as anti-HLA-DR reagents without platelet absorption. Of the 219 positive sera 51 contained defined anti-DR antibodies (20 monospecific and 31 bi- or multispecific). The 13 best sera recognized DR1 and DR7 specificities with r values from 0.83 to 1. Twenty-four sera selected by CF were also studied by lymphocytotoxicity technique against peripheral blood B lymphocytes (B-LCT). Both PHA-CF and B-LCT techniques gave similar results, detecting the same specificities and showing comparable sensitivity. The advantages of CF are: easy storage of target cells at -80 degrees C or + 4 degrees C, and fast reading. For these reasons PHA-CF or CF on cultured B lymphoid cell lines can be proposed for large scale screening of anti-HLA-DR sera. The sera thus screened can be used for HLA-DR typing either by PHA-CF or B-LCT.

Antibodies↗
PubMed1980

[Kinetics of the appearance of HLA-DR antigens on human alloactivated T lymphocytes and the demonstration of new antigenic determinants].

By studying serologically the appearance of HLA-DR determinants on T lymphocytes activated by a mixed lymphocyte culture, we have been able to demonstrate the existence of a new class of antigenic determinants distinct from classical HLA-DR antigens. Indeed, some monospecific anti-DR sera were cytotoxic from some alloactivated T cells, though not directed against their HLA-DR specificity. The absorption of these anti-sera on B lymphocytes bearing the HLA-DR antigen against which they were directed, did not remove their reactivity on alloactivated T lymphocytes. The absorption of the same anti-sera on activated T lymphocytes did not affect their anti-DR reactivity. This study shows the existence of new antigenic determinants expressed by T lymphocytes during their activation: alloactivated T lymphocyte antigens (AATL).

Cells, Cultured↗
PubMed1980

Functional study and detection of HLA-D products on fractionated human bone marrow cells.

Bone marrow cells from nine normal human volunteers obtained from the Iliac crest, were used in this work for antigen determination and functional studies. The bone marrow aspirated cells were sequentially separated: elimination of erythrocyte, granulocytes and monocytes achieved by Ficoll-Isopaque centrifugation followed by plastic adherence. Purified bone marrow cells were finally separated by size using velocity sedimentation. The slow sedimenting small cells were shown to be mainly T lymphocytes, probably of blood origin. The medium sized bone marrow cells were shown to contain myeloid precursors (CFu-c). Large immature cells were in cycle actively synthesizing DNA molecules. HLA-D and HLA-DR detections on the fractionated cells were performed using three techniques: fluorescence with specific anti HLA-DR allo and xeno antisera; primed lymphocyte typing (PLT) with anti HLA-DR monospecific in vitro primed lymphocytes and detection of the HLA-D stimulating product using the bone marrow fractionated cells as stimulators in a mixed leukocyte culture. Concordant results were obtained with the three techniques. Lymphocytes in the bone marrow express HLA-D products a peripheral lymphocytes. Bone marrow fractions depleted of lymphocytes and monocytes also contain approximately 20% of cells expressing HLA-D products The meaning of the expression of HLA-D products on immature precursors non-lymphoid cells is discussed.

Bone Marrow Cells↗
PubMed1978

Some chronic lymphocytic leukemia cells bearing surface immunoglobulins share determinants with T cells.

One set of antigens is common to some chronic lymphocytic leukemia (CLL) cells bearing surface immunoglobulins (Ig) and normal T cells. Proliferating cells from thirty-eight patients were studied with four antisera recognizing normal human T but not B cells. These antisera were raised in rabbits against (a) Sezary cells, (b) blood lymphocytes from a patient with sex-linked agammaglobulinemia, (c) T lymphoblasts and (d) thymus cells. In four CLL cases, the cells expressed the receptor for sheep erythrocytes and lacked surface Ig. Cells from thirty-four CLL cases bore monoclonal surface Ig and did not bind sheep erythrocytes. Twelve out of these thirty-four cases of CLL had cells which were lysed by one or, more frequently, by the four anti-human T cell xenoantisera. By absorption experiments, one set of at least three antigens common to the cells of some of these CLL and T cells was defined. Depending on the patient, the cells can either carry one, some or all of the antigens of this set. However, it was also demonstrated by absorption that these cells lacked antigens particular to the T cell lineage, while the cells from T CLL cases carried both sets of antigens.

Animals↗
PubMed1978

Anti-B cell lymphocytotoxic antibodies in kidney transplant recipients.

Serial serum samples from 47 renal allotransplant recipients were screened for antiperipheral blood lymphocyte, anti-B cell, and anti-Daudi cell line antibodies. Various associations of these antibodies were observed in 28 patients. Anti-Daudi did not correlate with graft survival, whereas anti-B, although they were often associated with anti-peripheral blood lymphocyte antibodies, showed the strongest correlation with chronic rejection (P = 0.00002). However anti-B cytotoxicity preceded or was concurrent with the onset of chronic rejection in only 53% of the cases. Antibodies were absent in six of nine patients with irreversible acute rejection, but they usually appeared after transplant nephrectomy. These findings suggest that anti-B cell antibodies may play a role in the rejection process. In 15 of 17 recipients (88%), anti-B cell antibodies occurred during the first trimester after transplantation. These patients showed 20% 1-year graft survival compared with 68% in those without antibodies at that time (P less than 0.005).

Antibodies↗