A comparison of EpsteinBarr virus copy number on MLNs in our system for the effective acquisition of tolerance

MLNs may be susceptible to excess IL-4 production and thus maintain inflammation in the context of continuous administration of food allergens, even though strong systemic tolerance was induced. By further LEE011 improvement, the OVA23-3 mouse model may facilitate delineation of the decisional factors in the blunted T-cell immune responses against oral administered antigens that subsequently cause inflammation versus tolerance. In addition, because antigen-specific T-cells may play an important role in triggering and driving IgE-mediated diarrhea, clarifying the mechanism underlying the T-cell mediated intestinal inflammation and developing ways to regulate T-cell responses in food allergy would promote the advancement of specific oral tolerance immunotherapy. Our study further suggests that systemic sensitization by routes other than the intestinal route is needed to induce severe IgEmediated systemic food-allergy like anaphylaxis. In conclusion in food allergy and to improve the induction of tolerance through rational strategies built on clarification of the mechanism, the persistent MLN-associated inflammatory responses must be controlled. However, our study clearly indicates that regulating immune responses in MLNs alone was insufficient, because both PPs and MLNs contribute to the development of the T-cell mediated intestinal inflammation of food allergy. In this regard, PPs are the early and direct inductive sites of immune responses on the intestinal epithelium for uptake of OVA. In addition, PPs reportedly uptake aggregated milk proteins and induce Th2 response. Therefore, regulation of the T-cells in PPs may, through the subsequent attenuation of persistent MLN-driven inflammatory responses, be an easily accessible tool for treating or preventing the exacerbation of intestinal inflammation. An M-celltargeting delivery system or tolerogenic dendritic cell induction techniques may be valuable in cases involving soluble antigens, such as OVA. Epstein-Barr virus is a ubiquitous human gammaherpesvirus. Following primary infection EBV establishes lifelong persistent infection through latent infection of memory B cells where the virus genome is transcriptionally silent. Reactivation from latency is required for the production of infectious EBV, with such lytic EBV replication being under the control of host and virus factors. In particular, terminal differentiation of memory B cells into plasma cells can lead to EBV lytic reactivation. The mechanisms of host induction of EBV lytic replication are incompletely understood, but periodic shedding of EBV in saliva and variation in saliva virus load between people suggest host genetic variation may contribute to EBV lytic cycle induction. Lymphoblastoid cell lines are human B cells immortalised in vitro by EBV and are a useful model of latent infection of B cells. Previous studies on LCLs have shown that when multiple LCLs are derived from the same individual, inter-individual variation in EBV copy number in LCLs is greater than intraindividual variation. A study of the impact of EBV copy number on the gene expression profiles of 198 HapMap LCLs reported that expression of 125 human genes was significantly correlated with EBV copy number.

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