Renal ischemia-reperfusion injury (IRI) after kidney transplantation is a major cause of delayed graft function. Even though IRI is recognized as a highly coordinated and specific process, the pathways and mechanisms through which the innate response is activated are poorly understood. In this study, we used a mouse model of acute kidney IRI to examine whether the interactions of costimulatory receptor CD137 and its ligand (CD137L) are involved in the early phase of acute kidney inflammation caused by IRI. We report here that the specific expressions of CD137 on natural killer cells and of CD137L on tubular epithelial cells (TECs) are required for acute kidney IRI. Reverse signaling through CD137L in TECs results in their production of the chemokine (C-X-C motif) receptor 2 ligands CXCL1 and CXCL2 and the subsequent induction of neutrophil recruitment, resulting in a cascade of proinflammatory events during kidney IRI. Our findings identify an innate pathogenic pathway for renal IRI involving the natural killer cell-TECneutrophil axis, whereby CD137-CD137L interactions provide the causal contribution of epithelial cell dysregulation to renal IRI. The CD137L reverse signaling pathway in epithelial cells therefore may represent a good target for blocking the initial stage of inflammatory diseases, including renal IRI.acute inflammation | costimulatory ligand

Anti-4-1BB-mediated anticancer effects were potentiated by depletion of CD4 + cells in B16F10 melanoma-bearing C57BL/6 mice. Anti-4-1BB induced the expansion and differentiation of polyclonal tumor-specific CD8 + T cells into IFN-;-producing CD11c + CD8 + T cells. The CD4 + cell depletion was responsible for facilitating immune cell infiltration into tumor tissues and removing some regulatory barriers such as T regulatory and indoleamine-2,3-dioxygenase (IDO) + dendritic cells. Both monoclonal antibodies (mAb) contributed to the efficient induction of MHC class I molecules on the tumor cells in vivo. The effectors that mediated the anti-4-1BB effect were NKG2D + KLRG1 + CD11c + CD8 + T cells that accumulated preferentially in the tumor tissues. Blocking NKG2D reduced the therapeutic effect by 20% to 26%, which may indicate that NKG2D contributes partially to tumor killing by the differentiated CD8 + T cells. Our results indicate that the combination of the two mAbs, agonistic anti-4-1BB and depleting anti-CD4, results in enhanced production of efficient tumor-killing CTLs, facilitation of their infiltration, and production of a susceptible tumor microenvironment. [Cancer Res 2007;67(18):8891-9]

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Summary The glucocorticoid‐induced tumour necrosis factor receptor family related gene (GITR) has been reported to be expressed on the activated T and CD4+CD25+ regulatory T cells (Treg). Signalling triggered by GITR not only neutralizes the suppressive effect of Treg cells, but also augments activation, proliferation and cytokine production of effector T cells. To test the role of GITR in 2,4,6‐trinitrobenzene sulphonic acid (TNBS)‐induced colitis − a murine model of mucosal inflammation − TNBS‐injected Balb/c mice were treated with agonistic anti‐GITR monoclonal antibody (mAb). Anti‐GITR treatment increased the death rate compared to rat IgG‐treated mice. Typically, death occurred within 4 days after the TNBS injection when the mice were treated with anti‐GITR. The mice that survived anti‐GITR treatment suffered from severe inflammation in their entire intestines. CD4+ T‐depletion protected the mice from colitis; even an anti‐GITR effect was not apparent. In contrast, CD8+ T depletion showed less protective than did CD4+ T depletion. Stimulation of GITR enhanced the production of proinflammatory cytokines including interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐12. It also enhanced the humoral response such as serum levels of IgG2b and IgA, which was completely dependent on CD4+ T cells. Taken together, this study demonstrated that GITR signalling on CD4+ T cells is involved in the development and progress of colitis by enhancing both T helper type 1 (Th1) and Th2 type responses.

A strain sensor system based on optical fiber Bragg gratings (FBGs) is proposed with a new matched-filter design. The strain variation on the sensor FBG is continuously followed and matched by a filter FBG by use of a feedback control loop that produces an identical strain condition on the filter FBG. The matched strain on the filter FBG is then determined from the resonance vibration of the fiber piece embedding the filter FBG. The implementation and the performance of the proposed system are described. It is demonstrated that the proposed system can distinguish strain variation on the sensor FBG with resolution of one microstrain.