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Recall Responses (recall + response)
Selected AbstractsImmunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Clifton O. Bingham III Objective To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab-induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell,dependent antigen), pneumococcal polysaccharide (T cell,independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity (DTH). Methods In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a ,4-fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to C albicans was measured 2,3 days following placement. Results Responses to tetanus toxoid vaccine (,4-fold rise) were similar in both groups (39.1% of rituximab-treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the C albicans skin test was comparable in both groups (77.4% of rituximab-treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab-treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2-fold rise in titer in response to ,1 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti-KLH IgG, compared with 93% of patients treated with MTX alone). Conclusion Recall responses to the T cell,dependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab-treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell,independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses. [source] Incomplete effector/memory differentiation of antigen-primed CD8+ T,cells in gene gun DNA-vaccinated miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Christina Bartholdy Abstract DNA vaccination is an efficient way to induce CD8+ T,cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class,I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to ,2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T,cells in uninfected mice differed from virus-primed CD8+ T,cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T,cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T,cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T,cells. [source] Establishment and recall of CD8+ T-cell memory in a model of localized transient infectionIMMUNOLOGICAL REVIEWS, Issue 1 2006Katherine Kedzierska Summary:, The influenza A virus model of localized, transient respiratory infection provides a well-defined experimental system for dissecting the induction and maintenance of CD8+ T-cell memory. This review focuses on quantitative and qualitative aspects of the prominent DbNP366 - and DbPA224 -specific CD8+ T-cell responses in virus-infected B6 mice. The different virus-specific effector and memory sets are compared by phenotypic [CD62L, interleukin-7 receptor-, (IL-7R,), and IL-15R, expression] and functional [interferon-, (IFN-,), tumor necrosis factor-, (TNF-,), and IL-2 production] analyses. Most clonotypes [defined by T-cell receptor (TCR) CDR3, sequence] generated during the acute phase of infection survive into memory, with those expressing the more consensus ,canonical' TCRs being the major contributors to the recall response. The extent of clonal expansion and the size of memory CD8+ T-cell populations has been characterized for mice challenged with either wildtype or mutant viruses, where broadly equivalent DbNP366 and DbPA224 expression was achieved by disabling the peptides in their native configuration, then expressing them in the viral neuraminidase protein. Combining the clonotypic and antigen dose analyses led to a somewhat mechanistic conclusion that the magnitude of any virus-specific CD8+ T-cell response will be a direct function of antigen dose and the size of the naïve or memory CD8+ T-cell precursor pool. [source] Identification of a dengue virus-specific HLA-A*0201-restricted CD8+ T cell epitopeJOURNAL OF MEDICAL VIROLOGY, Issue 4 2010Jinsheng Wen Abstract In this study, a combination of epitope-prediction programs and in vitro assays was used to identify dengue virus (DENV)-specific CD8+ T cell epitopes. Peripheral blood mononuclear cells (PBMCs) isolated from patients who recovered from dengue fever were stimulated with candidate epitope peptides derived from DENV, which were predicted by using SYFPEITHI and RANKpep epitope-prediction programs. The IFN-, ELISpot results and the results of intracellular staining of IFN-, showed that peptides NS4b_40 (TLYAVATTI), E_256 (QEGAMHTAL), NS3_205 (LPAIVREAI), NS5_210 (SRNSTHEMY), and NS3_207 (AIVREAIKR) could induce the recall response of CD8+ T cells. Furthermore, the results of the MHC,peptide complex stabilization assay revealed that peptide NS4b_40 (TLYAVATTI) has a high affinity for HLA-A*0201 molecules. The IFN-, ELISpot results and staining of intracellular IFN-, confirmed that this peptide could induce high-level CD8+ T cell response in HLA-A*0201 positive PBMCs. Peptide NS4b_40 (TLYAVATTI) was identified as a novel DENV-specific HLA-A*0201-restricted CD8+ T cell epitope. J. Med. Virol. 82:642,648, 2010. © 2010 Wiley-Liss, Inc. [source] T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008Karin L. Heckman Abstract By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb) shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner. The molecular determinants governing the ability of DC to reprogram the polarity of T cell recall responses are not yet known. In addition to the expected role of T-bet expressed by T cells in regulating Th1 responses, we find using in vitro assays and an established in vivo model of allergic airway inflammation that T-bet expression by DC is also required for the polarity shift promoted by B7-DC XAb. T-bet expression by both T cells and DC is critically important for B7-DC XAb-induced down-regulation of IL-4, up-regulation of IFN-, and suppression of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet expression in T-bet-deficient DC rescued their ability to modulate both naive and memory T-cell responses from Th2 to Th1. Our observations further our understanding of the critical mediators controlling the ability of DC to modify the responses of previously activated T cells and reveal the interesting use of the same transcription factor to regulate the inductive phenotype of DC and the inducible phenotype of T cells. [source] Glycolipid-activated NKT cells support the induction of persistent plasma cell responses and antibody titersEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Scott Devera Abstract NKT cell activation with CD1d-binding glycolipid ,-galactosylceramide (,-GC) enhances antibody responses to co-administered T-dependent antigen. The efficacy of ,-GC relative to other CD1d-binding glycolipids and adjuvants is not known. There is little information on how NKT cells affect antibody production beyond initial booster-stimulated recall responses. We therefore tested the hypothesis that ,-GC stimulates induction of plasma cells and antibody responses as effectively as Th1- and Th2-skewing variants of ,-GC and several other adjuvants. C57BL/6 and CD1d,/, mice were immunized with nitrophenol-conjugated keyhole limpet hemocyanin (NP-KLH) plus ,-GC or NP-KLH plus adjuvants before administration of an NP-KLH booster and assessing antibody responses and plasma cell frequency. ,-GC boosted long-term antibody responses as efficiently as all other agents tested and induced plasma cells that were detected in bone marrow 13,weeks after immunization. We then determined whether NKT cells were required in the presence of other adjuvants. CD1d,/, mice had a reduced induction of plasma cells in response to NP-KLH/Alum as compared to C57BL/6 mice. However, NKT cells were not required for the continued presence of those cells that were induced. Although NKT cells are capable of inducing persistent plasma cell responses, they may not play a major role in supporting longevity post-induction. [source] Fc,RII expression on follicular dendritic cells and immunoreceptor tyrosine-based inhibition motif signaling in B,cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2004Yüksel Aydar Abstract Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif (ITIM) signaling and inhibit B,cell activation by coligating B,cell receptor for antigen (BCR) and Fc,RII. Nevertheless, IC on follicular dendritic cells (FDC) stimulate rapid germinal center (GC) B,cell proliferation suggesting that interactions between IC and FDC render IC capable of B,cell activation. Tounderstand this, we studied the kinetics of FDC Fc,RII and complement receptors,1 and,2 (CR1&2) expressions during the GC reaction and determined whether FDC Fc,RII could bind Fc in IC and block ITIM signaling. Mice were immunized with sheep red blood cells (SRBC), and CR1&2 and Fc,RII levels in FDC reticula were monitored. The role of FDC Fc,RII was studied using anti-BCR-stimulated A20 cells. Levels of FDC Fc,RII in spleens of SRBC-injected mice increased within 24,h and were dramatically increased (,50-fold) on days,3 and,5. In contrast, CR1&2 levels increased less than twofold. Addition of normal FDC, but not FDC lacking Fc,RII, reduced and reversed anti-BCR-induced SH2 domain-containing inositol phosphatase (SHIP)-1 phosphorylation in A20 cells. FDC wereable to induce normal recall responses even after overnight incubation of the lymphocytes with IC to stimulate ITIM signaling. Engagement of Ig Fc with numerous Fc,RII on FDC appears to minimize IC-induced ITIM signaling. Thus, rapid up-regulation of FDC Fc,RII may explain why poorly immunogenic IC are rendered highly immunogenic when presented by FDC in GC. [source] Bifidobacterium animalis causes extensive duodenitis and mild colonic inflammation in monoassociated interleukin-10-deficient miceINFLAMMATORY BOWEL DISEASES, Issue 7 2009James P. Moran PhD Abstract Background: We recently showed that Bifidobacterium animalis is more prevalent within the colons of interleukin (IL)-10-deficient (,/,) mice than in wildtype (WT) animals colonized with the same specific pathogen-free (SPF) fecal contents. Here we tested the ability of this organism to cause T-cell-mediated intestinal inflammation by introducing it into germ-free (GF) IL-10,/, mice. Methods: GF IL-10,/, or WT mice were monoassociated with Bifidobacterium animalis subsp. animalis ATCC (American Type Culture Collection, Manassas, VA) 25527T or with B. infantis ATCC 15697T. Inflammation was measured by blinded histologic scores of the duodenum, cecum, and colon and by spontaneous secretion of IL-12/IL-23 p40 from colonic explants. Bacterial antigen-specific CD4+ mesenteric lymph node (MLN) T-cell recall responses were measured in response to antigen-presenting cells (APC) pulsed with bacterial lysates. Results:B. animalis caused marked duodenal inflammation and mild colitis in monoassociated IL-10,/, mice, whereas the intestinal tracts of WT animals remained free of inflammation. B. infantis colonization resulted in mild inflammation in the duodena of IL-10,/, mice. CD4+ MLN T cells from B. animalis monoassociated IL-10,/, mice secreted high levels of IFN-, and IL-17 in response to B. animalis lysate. B. animalis equally colonized the different intestinal regions of WT and IL-10,/, mice. Conclusions:B. animalis, a traditional probiotic species that is expanded in experimental colitis in this model, induces marked duodenal and mild colonic inflammation and TH1/TH17 immune responses when introduced alone into GF IL-10,/, mice. This suggests a potential pathogenic role for this commensal bacterial species in a susceptible host. (Inflamm Bowel Dis 2009) [source] Event frequency and children's suggestibility: a study of cued recall responsesAPPLIED COGNITIVE PSYCHOLOGY, Issue 7 2004Heather L. Price Research examining the effect of repeated experience on children's suggestibility for particular kinds of information has produced differing results. In one study, responses to recognition questions revealed heightened suggestibility for variable details in children who repeatedly experienced an event compared to children who experienced an event once. In other studies, no such effect was found with cued recall. In this study, 4,5-year old children engaged in one or four play sessions. Children were later given a biasing interview wherein half of the details were incorrectly represented. Children were then given a final memory test using free and cued recall prompts that was preceded by one of three instruction types: no special instructions, moderate instructions, or opposition instructions. Children in the repeated-event condition were more suggestible than those in the single-event condition, regardless of instructions. No significant differences in suggestibility were found across instructions conditions. Copyright © 2004 John Wiley & Sons, Ltd. [source] Breaking T cell tolerance against self type II collagen in HLA,DR4,transgenic mice and development of autoimmune arthritisARTHRITIS & RHEUMATISM, Issue 7 2010Tsvetelina Batsalova Objective To establish a new animal model in DRB1*0401 (DR4),transgenic mice in which T cell tolerance to self type II collagen (CII) can be broken and allow for the development of autoimmune arthritis, to investigate the role of posttranslational modifications of the CII259,273 epitope in the induction and breaking of tolerance of DR4-restricted T cells, and to characterize DR4-restricted T cell recognition of the immunodominant CII259,273 epitope. Methods DR4-transgenic mice expressing either the entire human CII protein (HuCII) or only the immunodominant T cell epitope of heterologous CII (MMC) in joint cartilage were established on different genetic backgrounds, and susceptibility to collagen-induced arthritis (CIA) was tested. Results HuCII mice displayed stronger T cell tolerance to heterologous CII than did MMC mice. On the B10 background, arthritis developed only in MMC mice with a defective oxidative burst. However, MMC mice on the C3H background were susceptible to arthritis also with a functional oxidative burst. Significant recall responses in tolerized mice were detected only against the nonglycosylated CII259,273 epitope. Recognition of the CII259,273 epitope was heterogeneous, but the majority of T cells in DR4 mice specifically recognized the nonglycosylated side chain of lysine at position 264. Conclusion It is possible to break tolerance to self CII and induce arthritis in DR4 mice. However, arthritis susceptibility is tightly controlled by the genetic background and by the source of the transgenic element for expressing the heterologous CII peptide as a self CII protein in the joint. In contrast to CIA in Aq -expressing mice, the nonglycosylated CII259,273 epitope is clearly immunodominant in both tolerized and nontolerized DR4 mice. [source] Effects of low-dose ultraviolet radiation on in vivo human cutaneous recall responsesAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2001Diona L Damian SUMMARY Relatively few studies have examined the effects of low-dose ultraviolet (UV) radiation on in vivo human cutaneous immunity, or the ability of sunscreens to prevent UV-induced immunosuppression. We have studied the effects of solar-simulated UV radiation on nickel contact hypersensitivity (CHS) in nickel-allergic volunteers, and on delayed type hypersensitivity responses in Mantoux-positive volunteers. Nickel CHS and Mantoux responses were significantly suppressed by acute, suberythemal UV exposures equivalent to less than 8 min summer sunlight. Both UVA and UVB wavebands were immunosuppressive, but UVA-induced immunosuppression was transient, whereas UVB had a more sustained effect. Dose,responses for UV immunosuppression were determined using the nickel method, enabling calculation of in vivo sunscreen immune protection factors in a manner analogous with sun protection factor measurement. Sunscreens were found to confer significantly less protection against UV-induced immunosuppression than against UV-induced erythema. [source] | ||||||||||