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Th1 Immune Response (th1 + immune_response)
Selected AbstractsAnti-inflammatory role of interleukin-15 in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2005Manuel A Silva MD Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source] CpG-containing ODN has a limited role in the protection against Toxoplasma gondiiPARASITE IMMUNOLOGY, Issue 2 2004R. Saavedra SUMMARY Bacterial DNA containing immunostimulatory motifs (CpG) induces the development of a TH1 immune response. Since protection against Toxoplasma gondii is correlated with this type of response, the aim of this work was to determine if a synthetic oligodeoxynucleotide (ODN) containing CpG sequences could be useful as adjuvant for the induction of a long-lasting protective immune response against T. gondii. BALB/c mice immunized with a total soluble antigen of T. gondii (TSA2) mixed with ODN-containing CpG sequences developed a typical TH1 response, as determined by antibody isotypes and interferon-, (IFN-,) and interleukin-4 (IL-4) production by spleen cells. However, they did not resist a challenge with the virulent RH strain of the parasite. Absence of protection paralleled with lower levels of IFN-,, when compared with mice vaccinated with the live tachyzoites of the attenuated ts.4 strain of the parasite, which resisted this challenge. Intraperitoneal injection of ODN alone to mice induced a high degree of resistance to a lethal challenge inoculated by the same route. Nevertheless, this nonspecific protection was transient. Thus, the use of ODN containing CpG motifs as adjuvant is of limited value for the induction of a protective immune response against T. gondii. [source] Notch1 expression on T,cells is not required for CD4+ T,helper differentiationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2004Fabienne Tacchini-Cottier Abstract Notch1 proteins are involved in binary cell fate decisions. To determine the role of Notch1 in the differentiation of CD4+ Th1 versus Th2 cells, we have compared T,helper polarization in vitro in naive CD4+ T,cells isolated from mice in which the N1 gene is specifically inactivated in all mature T,cells. Following activation, Notch1-deficient CD4+ T,cells transcribed and secreted IFN-, under Th1 conditions and IL-4 under Th2 conditions at levels similar to that of control CD4+ T,cells. These results show that Notch1 is dispensable for the development of Th1 and Th2 phenotypes in vitro. The requirement for Notch1 in Th1 differentiation in vivo was analyzed following inoculation of Leishmania major in mice with a T,cell-specific inactivation of the Notch1 gene. Following infection, these mice controlled parasite growth at the site of infection and healed their lesions. The mice developed a protective Th1 immune response characterized by high levels of IFN-, mRNA and protein and low levels of IL-4 mRNA with no IL-4 protein in their lymph node cells. Taken together, these results indicate that Notch1 is not critically involved in CD4+ T,helper,1 differentiation and in resolution of lesions following infection with L.,major. [source] Investigation of the Immunomodulatory Effects of Lactobacillus casei and Bifidobacterium lactis on Helicobacter pylori InfectionHELICOBACTER, Issue 3 2008Li Zhang Abstract Background:,Lactobacillus and Bifidobacterium species have shown beneficial effects in the treatment of Helicobacter pylori infection; however, the mechanisms behind such effects are not fully understood. In this study, we have investigated the immunomodulatory effects of probiotics in a mouse model of H. pylori infection. Materials and methods:,H. pylori -infected C57BL/6 mice were treated with L. casei L26, B. lactis B94, or no probiotics for 5 weeks, respectively. Mice not infected with H. pylori were included as normal controls. Gastric histology, protein levels of interleukin (IL)-1,, IL-10, IL-12/23p40, and H. pylori colonization density in the gastric tissues, as well as H. pylori -specific antibodies were examined. Results:, In mice receiving L. casei L26 and B. lactis B94, gastric neutrophil infiltration and IL-1, were significantly decreased and IL-10 was significantly increased as compared with mice receiving no probiotics. In mice receiving B. lactis B94, IL-12/23p40 was significantly increased and H. pylori IgG was significantly reduced as compared with mice receiving no probiotics. No significant difference of H. pylori colonization was observed among the three groups of mice. Conclusion:, The reduced level of IL-1, and neutrophil infiltration observed in mice infected with H. pylori following treatment with L. casei L26 and B. lactis B94 resulted from a modulation of immune response rather than a decrease of H. pylori colonization. Furthermore, B. lactis B94 has the intrinsic ability to promote a Th1 immune response through an increase in IL-12/IL-23. [source] Immune-expression of HSP27 and IL-10 in recurrent aphthous ulcerationJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2008Nelson T. Miyamoto Jr Background:, Recently, abnormal cellular immune response has been considered responsible for the oral lesion in the recurrent aphthous ulceration (RAU). For reasons not yet defined, antigens of the oral microbiota would trigger abnormal Th1 immune response against epithelial cells. On the other hand, studies have demonstrated that heat shock proteins (HSP) can block the production of proinflammatory cytokine through inhibition of NF-,B and mitogen-activated protein kinase pathways or activate anti-inflammatory cytokines and therefore control the magnitude of the immune response. HSP27 has been considered a powerful inductor of IL-10, a major inhibitor of Th1 response. Methods:, Using immunohistochemistry, we studied the expression and location of HSP27 and IL-10 in ulcerated lesions clinically diagnosed as RAU (n = 27) and to compare it with that of oral clinically normal mucosa (CT; n = 6) and of other inflammatory chronic diseases such as oral fibrous inflammatory hyperplasia (FIH; n = 18), Crohn's disease (CD; n = 10) and ulcerative colitis (UC; n = 9). Results:, A lower proportion of HSP27-positive epithelial cells in RAU and CD were observed when compared with CT and FIH (P < 0.001**; P = 0.013**). A lower proportion of IL-10-positive interstitial cells in RAU was observed when compared with FIH, UC, CT and CD (P < 0.001**; P < 0.001**; P < 0.001**; P = 0.034*). Conclusion:, Altogether the data suggest that a reduced cellular expression of HSP27 and IL-10 in RAU might be related with the aetiopathogenesis of the ulcerated oral lesions. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 3JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003F Terenghi Intravenous immunoglobulins (IVIg) are successfully used as immunomodulatory therapy in patients with multifocal motor neuropathy (MMN) but their mechanism of action remains unknown. An anti-idiotypic block of pathogenic autoantibodies has been often postulated even if other possible mechanisms, including a modulation of the release of various cytokines, have been proposed. To evaluate the expression of cytokines in patients with MMN and their possible modulation by IVIg, we determined circulating levels of TNF,, INF,, IL2, IL4, IL10, and IL12 by ELISA in serum samples of 17 patients with MMN and compared them with 12 patients with amyotrophic lateral sclerosis (ALS), 12 with multiple sclerosis (MS), 6 with chronic inflammatory demyelinating polyneuropathy (CIDP), 5 with myasthenia gravis (MG) and 12 healthy controls (NS). Comparable levels of INF,, IL2, IL4, IL10 and IL12 were detected in patients' sera and controls. Even if TNF, levels did not differ significantly among patients' groups, they were higher than in any healthy control (mean ± SD 1.2 ± 0.5 pg/ml, range 0.7,2.4 pg/ml), in 12 (70%) MMN patients (mean ± SD 3.6 ± 1.9 pg/ml; range 0.2,7.5 pg/ml), all ALS, 3 MS (25%), 2 CIDP (40%) and 2 MG (40%). We then measured the concentration of TNF, before and after IVIg therapy in 9 MMN and 2 ALS patients. In all but one MMN patients, circulating levels of TNF, slightly increased after treatment with IVIg (mean values 4.3 vs. 7.2 pg/ml) and decreased 3 weeks after therapy while in both ALS patients they decreased or remained unchanged. No detectable level of TNF, was found in IVIg preparation. This study shows that, similarly to what previously reported in other autoimmune neuropathy as GBS and CIDP, TNF, serum levels are slightly increased in MMN but, at odds with what reported in these disease, their concentration tend to increase parallel to clinical improvement after IVIg therapy. Further studies are necessary to clarify the pathogenetic implication of this finding and in particular whether a possible deviation from a presumably Th2 to a Th1 immune response may help explaining the effect of IVIg in MMN. [source] Distinct host-related dendritic cell responses during the early stage of Plasmodium yoelii infection in susceptible and resistant micePARASITE IMMUNOLOGY, Issue 5 2010W. ZHENG Summary The diverse outcomes of experimental murine infection with Plasmodium parasites, ranging from spontaneous cure to death, depend largely on the establishment of an effective Th1 immune response during the early stages of infection. However, the molecular and cellular factors responsible for the induction and regulation of this response are poorly understood. As immunity is initiated by dendritic cells (DCs), we compared their phenotype and function during the early stages of infection with Plasmodium yoelii 17XL (P.y 17XL) strain in susceptible (BALB/c) and resistant (DBA/2) mice. Resistant DBA/2 mice developed a greater number of myeloid (CD11c+CD11b+) and mature DCs, which were fully functional and capable of secreting IL-12p40. In contrast, susceptible BALB/c mice produced more plasmacytoid (CD11c+CD45R/B220+) and less mature DCs, resulting in high levels of IL-10 and TGF-,1. In addition, an in vitro experiment confirmed that splenic DCs from the two strains of mice differ in their ability to prime CD4+T cells in response to P.y 17XL stimulation. These findings indicate that the subset, the phenotype and the type of inflammatory and anti-inflammatory signals of splenic DCs are critical factors responsible for the discrepancy in the ability to induce or regulate Th1 immune responses in different hosts. [source] Endemically exposed asymptomatic individuals show no increase in the specific Leishmania (Viannia) panamensis -Th1 immune response in comparison to patients with localized cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 9-10 2002C. M. Trujillo SUMMARY In Colombia, most cases of human cutaneous leishmaniasis are caused by Leishmania (Viannia) panamensis. Interestingly, up to 30% of the exposed population do not suffer from clinical leishmaniasis although it is likely that they are continuously infected with Leishmania parasites. Since it is believed that the induction of efficient Th1 immune responses protects against Leishmania infections both in humans and in animal models, we determined if endemically exposed asymptomatics showed stronger Leishmania -specific Th1 immune responses than patients with active localized cutaneous leishmaniasis (LCL). We found that Montenegro skin test responses were slightly higher among asymptomatic individuals compared to patients suffering from LCL. However, PBMC from patients with LCL showed similar Leishmania -specific proliferative responses compared to PBMC from asymptomatic individuals. Furthermore, PBMC from both groups also secreted similar amounts of IFN-,, IL-12p40 and IL-10 after in vitro exposure to L. panamensis. No IL-4 was detected in the supernatants. Taken together our results suggest that lack of LCL development in endemically exposed asymptomatics cannot be explained by stronger systemic anti- Leishmania Th1 immune responses or decreased Th2 responses in these individuals in comparison to individuals who develop LCL. It may be possible that other mechanisms are responsible for resistance to cutaneous leishmaniasis in Colombia in endemically exposed asymptomatics. [source] Dendritic cell-derived IL-15 controls the induction of CD8 T,cell immune responsesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003René Rückert Abstract The development and the differentiation of CD8+ T,cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8+ T,cell-mediated Th1immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15,/,) mice or mice treated with soluble IL-15R, as an IL-15 antagonist showed significantly reduced CD8+ T,cell-dependent DTH responses, while activation of CD4+ T,cell and B,cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) fromIL-15+/+, IL-15,/, or IL-15R,,/, mice revealed that DC-derived IL-15 is an absolute requirement for the initiation of DTH response. The re-establishment of the interaction of IL-15 with the IL-15R, by incubating IL-15,/, DC with IL-15 completely restored the capacity to prime T,cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of pro-inflammatory cytokines by DC and triggered in vitro CD8+ T,cell proliferation and IL-2 release. Taken together, the data suggest that an autocrine IL-15/IL-15R, signaling loop in DC is essential for inducing CD8+ -dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeuticmodulation of clinically relevant DTH reactions. [source] Distinct host-related dendritic cell responses during the early stage of Plasmodium yoelii infection in susceptible and resistant micePARASITE IMMUNOLOGY, Issue 5 2010W. ZHENG Summary The diverse outcomes of experimental murine infection with Plasmodium parasites, ranging from spontaneous cure to death, depend largely on the establishment of an effective Th1 immune response during the early stages of infection. However, the molecular and cellular factors responsible for the induction and regulation of this response are poorly understood. As immunity is initiated by dendritic cells (DCs), we compared their phenotype and function during the early stages of infection with Plasmodium yoelii 17XL (P.y 17XL) strain in susceptible (BALB/c) and resistant (DBA/2) mice. Resistant DBA/2 mice developed a greater number of myeloid (CD11c+CD11b+) and mature DCs, which were fully functional and capable of secreting IL-12p40. In contrast, susceptible BALB/c mice produced more plasmacytoid (CD11c+CD45R/B220+) and less mature DCs, resulting in high levels of IL-10 and TGF-,1. In addition, an in vitro experiment confirmed that splenic DCs from the two strains of mice differ in their ability to prime CD4+T cells in response to P.y 17XL stimulation. These findings indicate that the subset, the phenotype and the type of inflammatory and anti-inflammatory signals of splenic DCs are critical factors responsible for the discrepancy in the ability to induce or regulate Th1 immune responses in different hosts. [source] Endemically exposed asymptomatic individuals show no increase in the specific Leishmania (Viannia) panamensis -Th1 immune response in comparison to patients with localized cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 9-10 2002C. M. Trujillo SUMMARY In Colombia, most cases of human cutaneous leishmaniasis are caused by Leishmania (Viannia) panamensis. Interestingly, up to 30% of the exposed population do not suffer from clinical leishmaniasis although it is likely that they are continuously infected with Leishmania parasites. Since it is believed that the induction of efficient Th1 immune responses protects against Leishmania infections both in humans and in animal models, we determined if endemically exposed asymptomatics showed stronger Leishmania -specific Th1 immune responses than patients with active localized cutaneous leishmaniasis (LCL). We found that Montenegro skin test responses were slightly higher among asymptomatic individuals compared to patients suffering from LCL. However, PBMC from patients with LCL showed similar Leishmania -specific proliferative responses compared to PBMC from asymptomatic individuals. Furthermore, PBMC from both groups also secreted similar amounts of IFN-,, IL-12p40 and IL-10 after in vitro exposure to L. panamensis. No IL-4 was detected in the supernatants. Taken together our results suggest that lack of LCL development in endemically exposed asymptomatics cannot be explained by stronger systemic anti- Leishmania Th1 immune responses or decreased Th2 responses in these individuals in comparison to individuals who develop LCL. It may be possible that other mechanisms are responsible for resistance to cutaneous leishmaniasis in Colombia in endemically exposed asymptomatics. [source] | ||||||||||