Screening of 78 monoclonal antibodies directed against human leukocyte antigens for cross-reactivity with surface markers on canine lymphocytes.
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Animals↗
Biomedical subjects
J C Monier
Publications and source records attributed to J C Monier.
Induction of apoptosis in mouse thymocytes by cyclosporin A: in vivo study.
We investigated the in vivo effect of cyclosporin A (CsA) on mouse thymus and thymocytes. Administration of CsA (10 mg/kg of body weight) was found to induce a marked reduction in the size, weight and consistency of the thymus. These modifications were associated with thymic reticulo-epithelial cells (TREC) and thymocyte damage. Some of the damaged thymocytes displayed characteristic of cells undergoing apoptosis. Ultrastructural study of thymocytes and thymic tissue, as well as DNA electrophoresis of thymocytes, showed chromatin condensation, cellular shrinkage, and nuclear fragmentation in oligonucleosomal fragments. DNA labeling with propidium iodide (PI) of thymocytes from CsA treated mice cultured for 24 hrs showed an increased number of apoptotic nuclei. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific for thymocyte subsets confirmed that CsA induces a large decrease in the relative number of mature single positive (SP) CD4+CD8- and CD8+CD4- thymocytes expressing high densities of CD3 and T cell receptor ab (TCR alpha beta) surface molecules, but also a decrease in the absolute number of the other thymocyte subsets. These results suggest that CsA causes macroscopic and ultrastructural modifications of the thymus, associated with an active process of cell death in mouse thymocytes in vivo. In line with these results we formulate a hypothesis concerning the stage of T-cell development at which CsA induces apoptosis.
Animals↗
Induction of apoptosis in mouse thymocytes by cyclosporin A: an in vitro study.
The effect of cyclosporin A (CsA) on mouse thymocytes was investigated in vitro. Ultrastructural examination and DNA electrophoresis of 24hr-CsA-treated thymocytes showed chromatin condensation, cellular shrinkage and nuclear fragmentation in oligonucleosomal fragments. DNA labeling of CsA-treated-thymocytes with propidium iodide (PI) showed an increase in the number of apoptotic nuclei compared to untreated thymocytes. Furthermore, flow cytometric analysis using monoclonal antibodies (mAbs) specific to particular thymocyte subsets showed that CsA induces a decrease in the relative number of immature double positive (DP) CD4+CD8+ thymocytes in direct proportion to the concentration of CsA. No significant changes were observed in mature single positive (SP) CD4+CD8- and CD8+CD4- cells. Moreover, the cell viability of CsA-treated thymocytes was decreased. These results suggest that CsA induces the programmed cell death of thymocytes in vitro. Taken together with our previous study on the in vivo effect of CsA on mouse thymus and thymocytes, the present study confirms that, in addition to its effect on the thymic epithelium, CsA acts directly on thymocytes by inducing their programmed cell death. We postulate that immature DP thymocytes are the most likely targets of CsA.
Animals↗
[Cytoplasm antibodies of polynuclear neutrophils in Wegener's granulomatosis and systemic vasculitis].
In retrospective and prospective studies the sera of 442 patients recruited from an Internal Medicine department were examined by acetone indirect immunofluorescence and immunoblot in search of anti-neutrophil cytoplasm antibodies (ANCA). Twenty-three patients had Wegener's granulomatosis, and 419 had various control diseases including connective tissue diseases, vasculitis and granulomatosis. The sera from 100 healthy blood donors were used as controls. Among the 23 patients with generalized (n = 15) or localized (n = 8) Wegener's granulomatosis (active in 21/23), the indirect immunofluorescence test was positive in 92 percent of those with the generalized form and in 62 percent of those with the localized form. Nine of the 13 sera examined by immunoblot (69 percent) were positive (31 +/- 57 kDa bands). On the other hand, the sera from 38 (6.9 percent) patients with control diseases were positive at immunofluorescence: vasculitis (14 cases, 50 percent), connective tissue diseases (4 cases, 14.3 percent) and miscellaneous diseases including 3 neoplasms (10 cases, 35.7 percent). Only 6 of these 28 sera showed a 1/100th titer of ANCA. The sera of all healthy controls were negative. The sensitivity of ANCA for Wegener's granulomatosis at all stages was 72.2 percent, and its specificity 94.4 percent. This study confirms the value of ANCA as third diagnostic criterion of Wegener's granulomatosis, after the clinical and histological criteria.
Adolescent↗
IgM and IgA rheumatoid factors in canine polyarthritis.
IgM and IgA rheumatoid factor (RF) were detected by ELISA using a purified dog IgG as antigen in normal controls (N = 84), dogs with unclassified polyarthritis (N = 95), dogs with rheumatoid arthritis (RA) (N = 22), dogs with systemic lupus erythematosus (SLE) (N = 35), dogs with leishmaniasis or heart worm disease (N = 20) and dogs with pyometra (N = 16). Frequency and titre of IgM and IgA RF are low and comparable (P < 0.05) in dogs with unclassified polyarthritis or RA: respectively 24.2% and 27.3% for IgM RF and 21.0% and 18.2% for IgA RF; the mean titre being respectively 0.781 +/- 0.581 and 0.649 +/- 0.365 for IgM RF, and 0.774 +/- 1.331 and 0.740 +/- 1.169 for IgA RF. The frequencies of IgM and IgA RF are a little higher in dogs with SLE (IgM RF: 37.1%, IgA RF: 25.7%) and higher in dogs with leishmaniasis or heart worm disease (45.0% and 30.0%), especially in dogs with pyometra (68.7% and 37.5%). So, although dogs can produce IgM and IgA RF, these auto-antibodies are uncommon in dogs with RA. Furthermore, when RF are present their titre is much lower than in human RA.
Animals↗
Lack of anti-nuclear antibodies during HIV infection.
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Antibodies, Antinuclear↗
Canine systemic lupus erythematosus. I: A study of 75 cases.
We studied 75 cases of canine systemic lupus erythematosus (SLE) presenting with at least four criteria of the American Rheumatism Association (ARA), including antinuclear antibodies (ANAb). This disease mainly affects male German shepherds of an average age of 5 years. The most common clinical signs are polyarthritis (91% of cases), and renal (65%) and cutaneo-mucous disorders (60%). Hemolytic anemia is rare (13%). ANAb are present, often at high levels (> 256 up to 10(6) by indirect immunofluorescence on mouse blood smears). The titers are correlated with the severity and the stage of the disease. As double-stranded DNA Ab are rare and as antihistone Ab are frequent, the former could be replaced by the latter in the ARA criteria applied to the SLE dog. Another category of ANAb, named anti-type 1, also seems useful in diagnosing canine SLE. As for therapy, long-term remissions (up to 9 years without treatment) were obtained in 55.6% of 27 SLE dogs treated by levamisole. At first, levamisole was associated with induction corticotherapy, then administered alone and finally discontinued. Side effects were uncommon and transient.
Animals↗
Canine systemic lupus erythematosus. II: Antinuclear antibodies.
The frequency and the specificities of antinuclear antibodies (ANAb) were studied in dogs with systemic lupus erythematosus (SLE) and compared to those found in normal dogs and in dogs with various infectious diseases. Whole ANAb were detected by immunofluorescence. Anti-double-stranded DNA Ab were found in only 2% of SLE dogs, whereas anti-single-stranded DNA Ab were present in 21.4% of SLE dogs and in 26.8% of dogs with infectious disease. Antihistone Ab were frequently observed in SLE dogs (71%) and are essentially directed against trypsin-resistant epitopes of H3, H4 and H2A. The Western blots of nuclear extracts of HeLa cells were recognized mainly by type 1 Ab (30%, reacting with bands of 43, 36, 35, 34, 30 and 27 kDa) and by anti-Sm Ab (12%) associated with anti-RNP Ab. Anti-SSA and anti-SSB Ab were rare.
Animals↗
[Study of the immune profile of pregnant women].
During pregnancy, the fetus is an hemiallograft perfectly tolerated by the mother. With the aim of elucidating the mechanism of this tolerance, we have looked to see whether lymphocyte subsets are modified by pregnancy. Using monoclonal antibodies and flow cytometry, we have studied the changes in the immune profile of normal pregnant women and compared them with non pregnant women. In pregnant women, a significant decrease in the percentage of CD3+ cells is observed in the first trimester (61.1 +/- 14.7% versus 73.8 +/- 6.8%; p less than 0.001). The same data are obtained for CD4+ cells (38.2 +/- 10.7% versus 44.0 +/- 7.0%; p less than 0.05) and CD8+ cells (22.8 +/- 5.6% versus 28.0 +/- 8.9%; p less than 0.05). On the other hand, B lymphocytes (CD19+), monocytes (Leu M3+) and natural killer (NK) cells (Leu7+) remain stable during pregnancy. CD11a+ cells decreased during the 1st and 2nd trimesters. Lastly, activated T lymphocytes (CD3+DR+, CD8+DR+) are not modified. Using absolute numbers, a significant decrease is shown only for CD3+ cells in the 2nd and 3rd trimesters and for CD11a+ cells in the 2nd trimester of pregnancy. The decrease of T lymphocyte subsets, NK and CD11a+ cells during pregnancy partially explains the tolerance for the fetus.
Antigens, CD↗
Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies.
The in vivo effect of cyclosporin A (CsA) on the murine thymus was investigated by studying the ultrastructural cellular alterations, which are described for the first time, and the immunohistochemical modifications of thymocytes and thymic reticulo-epithelial cells (TREC). A marked reduction of the thymus size became apparent after 6 days of CsA treatment (10 mg/kg/day). Light microscopy studies using polyclonal antibodies (Ab) or monoclonal Ab specific to lymphoid sub-populations (anti-CD4, anti-CD5, anti-CD8), and specific to epithelial cells (anti-keratin: AKs, K8), to cortical TREC (TR4) and to subcapsular/medullary TREC (TR5, 3H9) showed that the number of CD4- 8+ or CD4+ 8- medullary thymocytes dramatically decreased and that the cortical TREC are affected, after 10 days of CsA treatment. These observations were confirmed by electron microscopy studies demonstrated that the medullary lymphoid population disappeared almost entirely. TREC, principally cortical type, presented signs of cellular lysis. A few cortical thymocytes showed some damage. At day 8 the medullary thymic tissue was disorganized, but no change was noted in the subcapsular area right up to the final day (day 10) of CsA treatment. These results suggest that CsA has a harmful effect on cortical TREC, which affects the development of immature thymocytes.
Animals↗
Systemic lupus erythematosus in dogs: association to the major histocompatibility complex class I antigen DLA-A7.
The DLA-A,B antigens and the allotypes of the fourth complement component have been determined in German shepherd dogs suffering from systemic lupus erythematosus. We have typed 26 unrelated affected dogs, 11 animals of a three generation family, and 16 dogs of a colony with a high frequency of the disease. The results obtained from the 26 unrelated diseased dogs were compared to those determined in the 23 unaffected German shepherds. The antigen DLA-A7 was found to be predominant in the diseased group with a c2 = 11.02, Pc = 0.02, and a relative risk for the carriers of 11.93. The antigens DLA-A1 and DLA-B5 were negatively associated to the disease (c2 = 14.95, Pc = 0.001, and c2 = 17.16, P = 0.0008 respectively) and thus may be of protective nature. These data were further substantiated by the typing of the three generation family and the colony.
Animals↗
Antinuclear antibodies: detection and diagnostic value.
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Amino Acyl-tRNA Synthetases↗
Human epithelial thymic tumours: heterogeneity in immunostaining of epithelial cell markers and thymic hormones.
Different hormones (thymulin, thymosin alpha 1, vasopressin), antigenic markers of cortical and subcapsular/medullary thymic areas and tumour associated antigens were studied on paraffin or frozen section and cultures of human epithelial thymic tumours ('thymomas'). Thymulin, thymosin alpha 1 and for the first time vasopressin are found in most tumours. The epithelial cells of five 'thymomas' had markers of both cortical (TE3) and subcapsular/medullary thymic regions (A2B5 and/or TE4 and/or anti-p19). Leu-7, a marker of subcapsular epithelial cells was positive only in two tumours. The histological classification into cortical and medullary tumours does not correspond to our immunofluorescence results. The presence of these markers does not support the theory of different embryologic origin of the cortical and subcapsular/medullary epithelial cells. Transferrin receptors were detected on only some epithelial cells of thymic 'carcinomas'. Adenocarcinoma related antigen and carcino embryonic antigen only stained a few epithelial cells of all the tumours. There is no expected correlation between the presence of epidermal growth factor receptors on cell membranes and the number of proliferative cells stained by the anti-Ki67 antibodies. Immunostainings were heterogeneous according to the epithelial thymic tumours, independent of histological classification and not yet useful for prognosis.
Adult↗
Heterogeneity of ribosomal autoantibodies from human, murine and canine connective tissue diseases.
Antiribosomal auto-antibodies (anti-Rib.Ab) have been studied in connective tissue diseases (human, dog and mouse) by immunoblotting after one-dimensional (1D) or two-dimensional (2D) gel electrophoresis of rat ribosomes. Anti-Rib.Ab could be found in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other connective tissue diseases (progressive systemic sclerosis, PSS; Sjögren syndrome, SjS; mixed connective tissue disease, MCTD; and dermatomyositis, DM with the frequencies 41.7%, 54.6% and 33%, respectively. Immunoblotting after 1D gel electrophoresis showed the great heterogeneity of ribosomal proteins recognized by the anti-Rib.Ab. In the SLE, however, the most frequent antibodies stained bands of the 40S subunit: 30 kDa (34% of positive sera), 19.5 kDa (24.5%) and 43 kDa (17%). In RA, the 25-kDa band of the 60S subunit was the most common (54% of positive sera). In the other human connective tissue diseases, there was no particular predominance. In the MRL/1, anti-Rib.Ab were very frequent (92.6%). The 43-kDa band of the 40S subunit was found in 100% of positive sera. Seventeen out of nineteen dogs with SLE gave positive results on immunoblot, and all of them stained the 43-kDa band of the 40S subunit. 2D gel electrophoresis gave identification of Po, L7, L5, Sb, S19, S13 and L2 proteins in SLE, S3 and SjS, L35a and L37a in RA, and L7, S6 and/or L7a in MRL/1.
Animals↗
The effect of histamine on the induction of experimental autoimmune hemolytic anemia on OF1, BALB/c and SJL mice.
Erythrocyte autoantibodies can be elicited in mice by injection of rat red blood cells (RBC) which are cross-reactive with mouse RBC. In this report, we show that histamine injected in vivo delayed the production of autoantibodies among BALB/c and OF1 mice. In contrast, the induction of autoantibodies in SJL mice was not affected by histamine. Furthermore, histamine did not affect the production of anti-rat RBC. Cimetidine (anti-H2) but not diphenhydramine (anti-H1) inhibited the histamine effect.
Anemia, Hemolytic, Autoimmune↗
Antinuclear antibodies detected by indirect immunofluorescence on HEp2 cells and by immunoblotting in patients with systemic sclerosis.
The HEp2 cell cultures appeared highly sensitive in detecting the antinuclear antibodies (ANAb) in systemic sclerosis, principally anticentromere antibodies of the CREST syndrome. The immunoblotting used with either complex cellular extracts from HeLa and rabbit thymus or purified nuclear components (high mobility group (HMG) proteins and histones) is able to identify precisely the ANAb targets and to contribute to diagnosis. With nuclear extracts of HeLa cells, the sera from 75.8% of CREST syndrome subjects stained 18 and 22 kD proteins. Corresponding antibodies were also detected in 72.7% of these patients, on HEp2 centromers by indirect immunofluorescence. With the same extracts, 33.3% of sera from diffuse sclerosis/acrosclerosis patients contain antibodies staining 86, 73, 32 and 30kD. These sera also stain 77, 66 and 63kD from thymus extracts. Corresponding antibodies will be the anti-SCL-70 antibodies defined by double immunodiffusion. The anti-HMG antibodies were infrequent in systemic sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and consequently without interest for diagnosis. The anti-whole histones antibodies which are less frequent in diffuse sclerosis/acrosclerosis (35.7%) than in SLE (41.3%) recognize especially H1 and H2A in the first diseases, H1 and H2B in SLE and H1 and H3 in RA.
Adult↗
Study of a monoclonal antibody specific to epithelial cells of mammalian thymuses.
Hybridomas between spleen cells from BALB/c mice and Sp2/O-Ag14 mycloma cell line are performed by PEG fusion. An in vitro booster is realized with human thymic reticulo-epithelial cell cultures as antigen. A monoclonal antibody (3H9) directed against the thymic epithelium and stratified epithelia of mammals has been obtained and characterized.
Animals↗
Quantitative analysis of cultured thymic reticulo-epithelial cells labelled by different antibodies: a flow cytometric study.
Quantitative measurements of cultured human and murine thymic, and human thymoma reticuloepithelial cells (REC), immunolabeled by different antibodies (Ab) (TE3, TE4, anti-HTLV p19(p19), lu5, K11 and Aks) and by thymic hormones (thymulin and thymosin alpha 1 (Ta1)) within these cells, were performed using a flow cytometric technique. The anti-keratin polyclonal Ab labeled nearly the whole human or murine population. The p19 monoclonal Ab (MoAb), specific for the subcortical/medullary thymic regions, labelled 37-77% of the human REC. The TE3 MoAb, specific for the cortical region, labelled 54-83% of the REC. These percentages suggest that the cultured thymic REC (TREC) had markers of both regions together and therefore that these markers are not absolutely specific to determine their subcortical/medullary or cortical thymic origin. For the three populations there were more cells containing Ta1 than thymulin. The overlap of the percentage of labelled cells suggests that the same cell could synthesize the two hormones and that these hormones could be localized within the TE3 positive cells.
Animals↗