Fatima Sardi | Université Paris Descartes (original) (raw)

Papers by Fatima Sardi

Research paper thumbnail of Therapy with anti-TNFα antibody enhances number and function of Foxp3+ regulatory T cells in inflammatory bowel diseases

Inflamm Bowel Dis, 2010

Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of ... more Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4(+) CD25(+) Foxp3(+) T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFα antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs. Active IBD patients including 16 with Crohn's disease and 9 with ulcerative colitis were treated with anti-TNFα mAb. PBMCs were harvested immediately before and 2 weeks after the first injection. The frequency and phenotype of circulating CD4(+) CD25(+) Foxp3(+) Tregs were analyzed by flow cytometry, and their suppressive function was assessed by the ability of purified CD4(+) CD25(+) CD127(-) Tregs to inhibit the proliferation of allogenic CD4(+) CD25(-) Teffs. CD4(+) CD25(+) Foxp3(+) Treg frequency was significantly lower in active IBD patients than in controls (2.8% ± 0.4% vs. 4.6% ± 0.6%, respectively; P = 0.01). On day 14 following the first anti-TNFα infusion, the frequency of circulating Tregs was significantly enhanced in IBD patients (4.0% ± 0.5% vs. 2.8% ± 0.4%, before treatment; P = 0.001), with a 2- to 3-fold increase in the intensity of Foxp3 expression. In addition, infliximab treatment enhanced the suppressive function of circulating Tregs, as shown by inhibition of Teff proliferation at a 1:8 Treg/Teff ratio (28% ± 5% vs. 66% ± 10%, after treatment; P = 0.04). These data demonstrate that anti-TNFα treatment of active IBD rapidly enhances the frequency of functional Foxp3(+) Tregs in blood and potentiates their suppressive function. This indicates that Treg potentiation may represent an unanticipated outcome of anti-TNFα biotherapy in IBD.

Research paper thumbnail of CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

The Journal of Immunology, 2009

Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in... more Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4(+) T cells to control colitis, we used our model of CD8(+) T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4(+) T cells in MHC class II-deficient (Abeta(degrees/degrees)) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-gamma-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant C57BL/6 strain. Cotransfer experiments in RAG2(degrees/degrees) mice and ex vivo studies showed that CD4(+)CD25(+) T cells completely prevented CD8(+) T cell-mediated colitis and controlled CD8(+) T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4(+) regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8(+) T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased the suppressive function of Foxp3(+)CD4(+) regulatory T cells of colon lamina propria. These data demonstrate that CD4(+) regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8(+) T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8(+) effectors.

Research paper thumbnail of Blockade of LTB4/BLT1 pathway improves CD8+ T-cell-mediated colitis

Inflammatory Bowel Diseases, 2011

Background: Leukotriene B4 (LTB 4 ) has chemotactic properties for activated T cells expressing t... more Background: Leukotriene B4 (LTB 4 ) has chemotactic properties for activated T cells expressing the high-affinity receptor BLT 1 . This study investigated whether the LTB 4 antagonist (CP-105,693), selective for BLT 1 receptor, could protect mice from colitis mediated by specific cytotoxic CD8 þ T lymphocytes (CTL).

Research paper thumbnail of Therapy with anti-TNFα antibody enhances number and function of Foxp3+ regulatory T cells in inflammatory bowel diseases

Inflammatory Bowel Diseases, 2011

Background: Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFa, hyperac... more Background: Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFa, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4 þ CD25 þ Foxp3 þ T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFa antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs.

Research paper thumbnail of W1803 Therapy With Anti-TNFα Antibody Enhances Number and Function of FOXP3+ Regulatory T Cells in Inflammatory Bowel Diseases

Research paper thumbnail of M1794 Effects of TNFα on the Phenotype and the Function of Regulatory T Cells: Implications for Crohn's Disease

Gastroenterology, 2010

blood and lamina propria of IBD patients and healthy controls, and stimulated with IL-27 In Vitro... more blood and lamina propria of IBD patients and healthy controls, and stimulated with IL-27 In Vitro for 48h, cytokine levels were examined by ELISA and real-time PCR, and RORC mRNA expression was analyzed by real time PCR. Results: Expression of IL-27p28 and IL-27R mRNA in intestinal mucosa of CD patients was significantly higher compared with UC patients and healthy controls (P < 0.01). Western blotting analysis demonstrated that level of IL-27p28 protein in intestinal mucosa of CD patients was also significantly higher than UC patients and healthy controls (P < 0.05). PB-or LP-CD4 + T cells from IBD patients produced lower levels of TNF and IFN-gamma than controls when stimulated with IL-27 and anti-CD3 mAb. Importantly, IL-27 downregulated IBD CD4 + T cells to differentiate into Th17 cells, as characterized by decreased expression of IL-17A and RORC. Conclusions: IL-27p28 is increased expression in inflamed mucosa of IBD and may inhibit Th17 cell differentiation in inflamed mucosa. This work implies that IL-27 is involved in the pathogenesis of IBD and may have a therapeutic potential in IBD.

Research paper thumbnail of Therapy with anti-TNFα antibody enhances number and function of Foxp3+ regulatory T cells in inflammatory bowel diseases

Inflamm Bowel Dis, 2010

Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of ... more Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4(+) CD25(+) Foxp3(+) T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFα antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs. Active IBD patients including 16 with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease and 9 with ulcerative colitis were treated with anti-TNFα mAb. PBMCs were harvested immediately before and 2 weeks after the first injection. The frequency and phenotype of circulating CD4(+) CD25(+) Foxp3(+) Tregs were analyzed by flow cytometry, and their suppressive function was assessed by the ability of purified CD4(+) CD25(+) CD127(-) Tregs to inhibit the proliferation of allogenic CD4(+) CD25(-) Teffs. CD4(+) CD25(+) Foxp3(+) Treg frequency was significantly lower in active IBD patients than in controls (2.8% ± 0.4% vs. 4.6% ± 0.6%, respectively; P = 0.01). On day 14 following the first anti-TNFα infusion, the frequency of circulating Tregs was significantly enhanced in IBD patients (4.0% ± 0.5% vs. 2.8% ± 0.4%, before treatment; P = 0.001), with a 2- to 3-fold increase in the intensity of Foxp3 expression. In addition, infliximab treatment enhanced the suppressive function of circulating Tregs, as shown by inhibition of Teff proliferation at a 1:8 Treg/Teff ratio (28% ± 5% vs. 66% ± 10%, after treatment; P = 0.04). These data demonstrate that anti-TNFα treatment of active IBD rapidly enhances the frequency of functional Foxp3(+) Tregs in blood and potentiates their suppressive function. This indicates that Treg potentiation may represent an unanticipated outcome of anti-TNFα biotherapy in IBD.

Research paper thumbnail of CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T Cells

The Journal of Immunology, 2009

Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in... more Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4(+) T cells to control colitis, we used our model of CD8(+) T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4(+) T cells in MHC class II-deficient (Abeta(degrees/degrees)) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-gamma-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant C57BL/6 strain. Cotransfer experiments in RAG2(degrees/degrees) mice and ex vivo studies showed that CD4(+)CD25(+) T cells completely prevented CD8(+) T cell-mediated colitis and controlled CD8(+) T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4(+) regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8(+) T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased the suppressive function of Foxp3(+)CD4(+) regulatory T cells of colon lamina propria. These data demonstrate that CD4(+) regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8(+) T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8(+) effectors.

Research paper thumbnail of Blockade of LTB4/BLT1 pathway improves CD8+ T-cell-mediated colitis

Inflammatory Bowel Diseases, 2011

Background: Leukotriene B4 (LTB 4 ) has chemotactic properties for activated T cells expressing t... more Background: Leukotriene B4 (LTB 4 ) has chemotactic properties for activated T cells expressing the high-affinity receptor BLT 1 . This study investigated whether the LTB 4 antagonist (CP-105,693), selective for BLT 1 receptor, could protect mice from colitis mediated by specific cytotoxic CD8 þ T lymphocytes (CTL).

Research paper thumbnail of Therapy with anti-TNFα antibody enhances number and function of Foxp3+ regulatory T cells in inflammatory bowel diseases

Inflammatory Bowel Diseases, 2011

Background: Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFa, hyperac... more Background: Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFa, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4 þ CD25 þ Foxp3 þ T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFa antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs.

Research paper thumbnail of W1803 Therapy With Anti-TNFα Antibody Enhances Number and Function of FOXP3+ Regulatory T Cells in Inflammatory Bowel Diseases

Research paper thumbnail of M1794 Effects of TNFα on the Phenotype and the Function of Regulatory T Cells: Implications for Crohn's Disease

Gastroenterology, 2010

blood and lamina propria of IBD patients and healthy controls, and stimulated with IL-27 In Vitro... more blood and lamina propria of IBD patients and healthy controls, and stimulated with IL-27 In Vitro for 48h, cytokine levels were examined by ELISA and real-time PCR, and RORC mRNA expression was analyzed by real time PCR. Results: Expression of IL-27p28 and IL-27R mRNA in intestinal mucosa of CD patients was significantly higher compared with UC patients and healthy controls (P < 0.01). Western blotting analysis demonstrated that level of IL-27p28 protein in intestinal mucosa of CD patients was also significantly higher than UC patients and healthy controls (P < 0.05). PB-or LP-CD4 + T cells from IBD patients produced lower levels of TNF and IFN-gamma than controls when stimulated with IL-27 and anti-CD3 mAb. Importantly, IL-27 downregulated IBD CD4 + T cells to differentiate into Th17 cells, as characterized by decreased expression of IL-17A and RORC. Conclusions: IL-27p28 is increased expression in inflamed mucosa of IBD and may inhibit Th17 cell differentiation in inflamed mucosa. This work implies that IL-27 is involved in the pathogenesis of IBD and may have a therapeutic potential in IBD.