Compartmentalization of total and virus-specific tissue-resident memory CD8+ T Cells in human lymphoid organs

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections

Epistaxis risk associated with intranasal corticosteroid sprays: a systematic review and meta-analysis

Objective: Intranasal corticosteroids (INCSs) are widely utilized for the treatment of allergic rhinitis. Epistaxis is a known adverse effect of INCSs, but it is not known if the risk of epistaxis differs among INCSs. Data Sources: Systematic review of primary studies identified through Medline, Embase, Web of Science, PubMed Central, and Cochrane databases. Review Methods: Systematic review was conducted according to the PRISMA standard. English-language studies were queried through February 1, 2018. The search identified randomized controlled trials of INCSs for treatment of allergic rhinitis that reported incidence of epistaxis. An itemized assessment of the risk of bias was conducted for each included study, and meta-analysis was performed of the relative risk of epistaxis for each INCS. Results: Of 949 identified studies, 72 met the criteria for analysis. Meta-analysis demonstrated an overall relative risk of epistaxis of 1.48 (95% CI, 1.32-1.67) for all INCSs. The INCSs associated with the highest risk of epistaxis were beclomethasone hydrofluoroalkane, fluticasone furoate, mometasone furoate, and fluticasone propionate. Beclomethasone aqueous, ciclesonide hydrofluoroalkane, and ciclesonide aqueous were associated with the lowest risk of epistaxis. Conclusions about epistaxis with use of budesonide, triamcinolone, and flunisolide are limited due to the low number of studies and high heterogeneity. Conclusions: While a differential effect on epistaxis among INCS agents is not clearly demonstrated, this meta-analysis does confirm an increased risk of epistaxis for patients using INCSs as compared with placebo for treatment of allergic rhinitis