No abstract

In order to determine the role of CD4+ and CD8+ T-cells and of interleukin-5 (IL-5) in causing antigen-induced eosinophil infiltration into the site of airway late-phase reaction, we examined the effect of the in vivo depletion of CD4+ and CD8+ T-cells on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. We also studied the effect of anti-murine IL-5 monoclonal antibody (mAb) on the antigen-induced eosinophil infiltration in the trachea. The eosinophil infiltration into the trachea of ovalbumin (OVA)-sensitized BALB/c mice began to increase 9 h after OVA inhalation and persisted for more than 48 h. The in vivo depletion of CD4+ T-cells by pretreatment with anti-L3T4 mAb significantly decreased the eosinophil infiltration induced by OVA inhalation in the trachea of sensitized mice. However, the in vivo depletion of CD8+ T-cells by pretreatment with anti-Lyt-2 mAb had no significant effect on OVA-induced eosinophil infiltration in the trachea. Pretreatment with anti-murine IL-5 mAb also decreased OVA-induced eosinophil infiltration in the trachea. In contrast, neither disodium cromoglycate nor a selective antagonist for platelet-activating factor CV-6209 decreased OVA-induced airway eosinophilia in the mouse. Our results provide direct evidence that CD4+ but not CD8+ T-cells mediate antigen-induced eosinophil recruitment in the airways and that IL-5 mediates this eosinophil recruitment.

These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.

T regulatory cells (T regs ) can activate multiple suppressive mechanisms in vitro upon activation via the T cell receptor resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here, we found that antigen-specific T regs activated by dendritic cells (DCs) pulsed with two antigens suppressed T naive specific for both cognate and non-cognate antigens in vitro, but only suppressed T naive specific for cognate antigen in vivo. Antigen-specific T regs formed strong interactions with DC resulting in selective inhibition of the binding of T naive to cognate antigen, yet allowing bystander T naive access. Strong binding resulted in removal of the cognate peptide-MHCII (pMHCII) from the DC surface reducing the capacity of the DC to present antigen. The enhanced binding of T regs to DC coupled with their capacity to deplete pMHCII represents a novel pathway for T reg -mediated suppression and may be a mechanism by which T regs maintain immune homeostasis.

Mice homozygous for an autosomal recessive mutation aly (alymphoplasia) lack both lymph nodes and Peyer's patches, and show defects in both humoral and cellular immunity. Histopathological analysis revealed chronic inflammatory changes in exocrine organs such as the salivary gland, lacrimal gland, and pancreas of the homozygotes (aly/aly), but not the heterozygotes (aly/+). In these exocrine organs, mononuclear cells consisting mainly of CD4+ T cells infiltrate periductal areas, and, in some cases, the cell infiltration extended to lobules. The inflammatory changes in exocrine organs were transferred by a T cell-enriched fraction of spleen cells from homozygous animals. These results suggest that autoimmune mechanisms mediated by self-reactive T cells may be involved in the inflammatory lesions of various exocrine organs in the homozygous mice, although these mice show immunodeficiency. Inflammatory changes were also observed in the lung of the homozygotes. Since Sjögren's syndrome is characterized by diffuse lymphocyte infiltration in the periductal areas of the lacrimal and salivary glands and is occasionally associated with pulmonary disease, aly/aly mice may serve as a unique spontaneous model of Sjögren's syndrome.

Objective. The aim of this prospective multicenter study was to identify biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with rheumatoid arthritis (RA).Methods. We recruited patients with RA who were treated with tocilizumab for the first time, and determined therapeutic responses at 6 months. In the training cohort (n ‫؍‬ 40), gene expression in peripheral blood mononuclear cells (PBMCs) at baseline was analyzed using genome-wide DNA microarray, with 41,000 probes derived from 19,416 genes. In the validation cohort (n ‫؍‬ 20), expression levels of the candidate genes in PBMCs at baseline were determined using real-time quantitative polymerase chain reaction (qPCR) analysis.Results. We identified 68 DNA microarray probes that showed significant differences in signal intensity between nonresponders and responders in the training cohort. Nineteen putative genes were selected, and a significant correlation between the DNA microarray signal intensity and the qPCR relative expression was confirmed in 15 genes. In the validation cohort, a significant difference in relative expression between nonresponders and responders was reproduced for 3 type I interferon response genes (IFI6, MX2, and OASL) and MT1G. Receiver operating characteristic curve analysis of models incorporating these genes showed that the maximum area under the curve was 0.947 in predicting a moderate or good response to tocilizumab in the validation cohort.Conclusion. Using genome-wide DNA microarray analyses, we identified candidate biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with RA. These findings suggest that type I interferon signaling and metallothioneins are involved in the pathophysiology of RA.Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, which

Objectives-To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS). Methods-Expression

SUMMARYIn order to determine regulatory mechanisms of eosinophil apoptosis, we examined the effect of recombinant IL-5 and interferon-gamma (IFN-°) on eosinophil apoptosis and bcl-2 expression. rhIL-5 (2 . 5 ng/ml) significantly inhibited eosinophil apoptosis in 96 h in vitro culture compared with medium only-cultured eosinophils (89 . 4