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S Jacquot

Publications and source records attributed to S Jacquot.

34 records · Page 2Linked to original sources
PubMed1997

CD27/CD70 interaction contributes to the activation and the function of human autoreactive CD27+ regulatory T cells.

CD27, a tumor necrosis factor receptor family member, is a constimulatory molecule for T and B cell activation. We demonstrate here that CD27 signaling is critical for T cell activation in the autologous mixed lymphocyte reaction (aMLR) and for aMLR-induced generation of regulatory T cells that suppress pokeweed mitogen-driven immunoglobulin G synthesis by B cells. Moreover, CD27, expressed on CD45RA+ CD4+ T cells, is directly involved in the suppressor function of aMLR-activated CD4+ T cells, probably by interfering with the interaction between CD70, the CD27 ligand, expressed on CD45RO+ CD4+ helper T cells, and CD27, expressed on B cells. CD8+ T cells, which are required in this system to obtain suppression, on the other hand, do not need CD27 engagement to exert their suppressor function.

Antigens, CD↗
PubMed1997

CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein.

Members of the tumor necrosis factor receptor (TNFR) superfamily are important for cell growth and survival. In addition to providing costimulatory signals for cell proliferation, ligation of both TNFR1 and Fas can result in programmed cell death or apoptosis. The underlying mechanism requires an intact 80-aa stretch present in the cytoplasmic tails of both TNFR1 and Fas, termed the death domain (DD). Here we show that CD27, a member of the TNFR family, expressed on discrete subpopulations of T and B cells and known to provide costimulatory signals for T and B cell proliferation and B cell Ig production, can also induce apoptosis. Co-crosslinking of surface Ig receptors along with ligation of CD27 augments CD27-mediated apoptosis. Unlike TNFR1 and Fas, the cytoplasmic tail of CD27 is relatively short and lacks the DD. Using the yeast two-hybrid system, we have cloned a novel protein (Siva) that binds to the CD27 cytoplasmic tail. It has a DD homology region, a box-B-like ring finger, and a zinc finger-like domain. Overexpression of Siva in various cell lines induces apoptosis, suggesting an important role for Siva in the CD27-transduced apoptotic pathway.

Amino Acid Sequence↗
PubMed1996

Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.

The Coffin-Lowry syndrome (CLS), an X-linked disorder, is characterized by severe psychomotor retardation, facial and digital dysmorphisms, and progressive skeletal deformations. Genetic linkage analysis mapped the CLS locus to an interval of 2-3 megabases at Xp22.2. The gene coding for Rsk-2, a member of the growth-factor-regulated protein kinases, maps within the candidate interval, and was tested as a candidate gene for CLS. Initial screening for mutations in the gene for Rsk-2 in 76 unrelated CLS patients revealed one intragenic deletion, a nonsense, two splice site, and two missense mutations. The two missenses affect sites critical for the function of Rsk-2. The mutated Rsk-2 proteins were found to be inactive in a S6 kinase assay. These findings provide direct evidence that abnormalities in the MAPK/RSK signalling pathway cause Coffin-Lowry syndrome.

Abnormalities, Multiple↗
PubMed1996

Enhanced CD3 monoclonal antibody induced proliferation of colonic mucosal T lymphocytes in Crohn's disease patients free of corticosteroid or immunosuppressor treatment.

Mucosal lymphocytes are increasingly activated in Crohn's disease. In order to investigate this phenomenon we tested the response of cultured colonic mucosal T lymphocytes to CD3 activation. These lymphocytes were obtained by biopsy from control subjects and Crohn's disease patients. T cells from mucosa involved in Crohn's disease showed a higher CD3-induced proliferative response compared to control T lymphocytes (P < 0.01). T cells from uninvolved areas showed a wide range of response, ranging from normal to very high proliferative indices. Our results suggest that the exaggerated response of mucosal T lymphocytes, due to the impairment of the downregulation of the CD3-dependent signaling process, may contribute to the pathogenesis of Crohn's disease.

Adult↗
PubMed1996

Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody.

BACKGROUND: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti-CD4 (B-F5) antibody in severe refractory Crohn's disease. METHODS: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B-F5 was given intravenously at a dose of 0.5 mg. day/kg for 7 consecutive days (patients 1-8). For patients 9-12, B-F5 was given at a dose of 0.5 mg. day/kg on the first day (day 0) and of 1 mg.day/kg on days 1-6. Follow-up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients. RESULTS: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed. CONCLUSION: In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.

Adolescent↗
PubMed1996

Association of HLA class II genes with susceptibility to Crohn's disease.

BACKGROUND: Published studies on the association between HLA class II genes and inflammatory bowel disease are contradictory perhaps because of the limited size and ethnic heterogeneity of the populations studied. AIM: To compare the frequencies of HLA class II genes in a large number of French patients with Crohn's disease and in an ethnically matched control group. METHODS: 344 patients (196 F, 148 M, mean age 23.6 years) with Crohn's disease were molecularly genotyped for the HLA-DQB1 and DRB1 alleles. The results were compared with those for an ethnically matched control population of 488 white adults. RESULTS: There were two significant variations of alleles at the DQB1 locus: an increase in DQB1*0501 allele frequency (chi 2 = 10.6, corrected p value (pc) = 0.01, odds ratio (OR) = 1.61) and a decrease in DQB1*0602/0603 allele frequencies (chi 2 = 8.43, pc = 0.037, OR = 0.66). DRB1 analysis showed associations with three allelic variations: an increase in the frequencies of DRB1*01 (chi 2 = 12.86, pc = 0.003, OR = 1.75) and DRB1*07 alleles (chi 2 = 11.18, pc = 0.008, OR = 1.58) and a very significant decrease in that of the DRB1*03 allele (chi 2 = 19.7, pc = 9.10(-5), OR = 0.46). CONCLUSION: The alleles DRB1*01 and DRB1*07 are associated with susceptibility to Crohn's disease. The strong negative association between the DRB1*03 allele and Crohn's disease suggests that the HLA-DRB1*03 allele mediates 'resistance' to Crohn's disease.

Adolescent↗
PubMed1995

CD27-CD70 interactions regulate B-cell activation by T cells.

CD27, a member of the tumor necrosis factor (TNF) receptor family, binds to its ligand CD70, a member of the TNF family, and subsequently induces T-cell costimulation and B-cell activation. CD27 is expressed on resting T and B cells, whereas CD70 is expressed on activated T and B cells. Utilizing transfected murine pre-B-cell lines expressing human CD27 or CD70, we have examined the effect of such transfectant cells on human B-cell IgG production and B-cell proliferation. We show that the addition of CD27-transfected cells to a T-cell-dependent, pokeweed mitogen-driven B-cell IgG synthesis system resulted in marked inhibition of IgG production, whereas the addition of CD70-transfected cells enhanced IgG production. The inhibition and enhancement of pokeweed mitogen-driven IgG production by CD27 and CD70 transfectants were abrogated by pretreatment with anti-CD27 and anti-CD70 monoclonal antibodies, respectively. In contrast, little or no inhibition of IgG production and B-cell proliferation was noted with CD27-transfected cells or either anti-CD27 or CD70 monoclonal antibody in a T-cell-independent Staphylococcus aureus/interleukin 2-driven B-cell activation system. In this same system CD70-transfected cells enhanced B-cell IgG production and B-cell proliferation, and this enhancement could be gradually abrogated by addition of increasing numbers of CD27-transfected cells. These results clearly demonstrate that interactions among subsets of T cells expressing CD27 and CD70 play a key role in regulating B-cell activation and immunoglobulin synthesis.

Antigens, CD↗
PubMed1994

Differential proliferative responses in subsets of human CD28+ cells delineated by BB27 mAb.

We report the identification of a novel 140 kDa disulfide-linked dimer expressed by a subset of peripheral blood T lymphocytes. This molecule, which is recognized by mAb BB27, is also detected on cells of the myelomonocytic lineage. In the T cell lineage, its expression is positively modulated after lymphocyte activation. A series of double-labeling experiments revealed that BB27 mAb identifies new CD4 and CD8 cell subsets different from those defined by CD45RA, CD45RO, CD26, CD29, CD31, and CD38. Finally, BB27 mAb also subdivides the CD28 subset. Of the utmost interest is the finding that a proliferative response to CD28 mAb and phorbol myristate acetate stimulation is exclusively obtained in the CD28+BB27+ cell subset, whereas the CD28+BB27- subset fails to proliferate.

Animals↗
PubMed1993

Antineutrophil cytoplasmic auto-antibodies in sera from patients with ulcerative colitis after proctocolectomy with ileo-anal anastomosis.

Presence of antineutrophil cytoplasmic auto-antibodies (ANCA) in ulcerative colitis could be an epiphenomenon related to colonic inflammation and/or may reflect a primitive disturbance of immune regulation. In this regard, study of ANCA status after the whole colorectal mucosa has been removed could favor one of these two hypothesis. We compared the prevalence of ANCA in a first group of 70 patients with non operated UC and in a second group of 32 patients with UC having had a proctocolectomy with ileoanal anastomosis. Perinuclear ANCA (p-ANCA) were found in 34/70 (49%) of the first group as compared to 11/32 (34%) in the second group (NS). Our results further support that the presence of ANCA in UC reflects an immune disturbance not linked to the presence of the target organ.

Adult↗
PubMedDate not supplied

Germline mosaicism in Coffin-Lowry syndrome.

We have identified a Coffin-Lowry syndrome pedigree where the disorder is associated with a novel splice site mutation in the RSK2 gene, leading to in-phase skipping of exon 5. Western blot analysis, using an antibody directed against the C-terminus of RSK2, failed to reveal RSK2 in this patient, suggesting strongly that the resulting internally deleted protein is unstable. The mutation was present in the DNA of one affected son and one manifesting daughter but was absent in two asymptomatic daughters, who carry the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results are consistent with the mutation arising as a postzygotic event in the mother, who therefore is a germinal mosaic. The application of linked markers to identify the disease allele for conventional genetic counselling would have been misleading in this family. This observation again highlights the importance of precise identification of the disease-causing mutation.

Abnormalities, Multiple↗