I) the retention of anti-tumor cytotoxicity of the genetically engineered cells at concentrations of temozolomide that upregulate tumor associated stress molecules that activate effector cell functions. Intra-cavity post-resection administration of gliomareactive genetically engineered cd T cells presents one of the few opportunities to deliver concentrated cellular immunotherapy directly to the site of residual malignancy at the time of maximal tumor vulnerability during high dose chemotherapy. The in vitro effectiveness of our cd T cell-based DRI strategy provides thenecessary foundation to pursue such an innovative approach to the treatment of high-grade gliomas.AcknowledgmentsWe would like to thank Arthur Nienhuis (St. Jude University, Memphis, TN) for the SIV vector system.Author ContributionsConceived and designed the experiments: LSL GYG HTS. Performed the experiments: JB AD YS 
AJ. Analyzed the data: LSL AD HTS. Contributed reagents/materials/analysis tools: LSL GYG HTS. Wrote the paper: LSL AD HTS.
Influenza A virus infection causes acute respiratory inflammation and leads to lethal diseases including hyper lung pneumonia. It is known that influenza A viruses initially infect air-way epithelial cells and induce hyper production of several cytokines or chemokines. These cellular products induce 
anti-viral effects including direct inhibition of viral replication or recruitment and buy PTH 1-34 activation of several immune cells, such as macrophages, neutrophils or lymphocytes to eliminate the viruses or virusinfected cells [1]. FasL is a specific ligand of Fas, which is a type-I trans-membrane protein to induce cell death [2]. Functional mutation of the FasL or Fas gene causes abnormal proliferation of peripheral lymphocytes [3]. In immunological events, it is proposed that FasL protein expressed on killer T or natural killer cells plays a role in effector function for eliminating virus-infected cells and at a late phase after the infection, FasL/Fas signaling is essential for the suicide FCCP mechanism for activated peripheral lymphocytes to terminate inflammation [2]. Recently, it has beenshown by DNA microarray analysis using mice infected with the highly pathogenic H1N1 influenza A virus (r1918 strain) comparing with the non-lethal virus (T691 strain) that induction of the expression of FasL/Fas signal related genes in the lung is associated with the mortality of mammalians after the infection [4]. It is also reported that influenza A virus infection induces cell death of the infected cells by Fas-dependent apoptosis [5]. More importantly, it has been demonstrated that FasL gene functionally mutated congenic B6Smn.C3-Tnfsf6gld/J mice are more resistant to lethal influenza virus infection than C57Bl/6J mice [6]. Other studies demonstrated that activation of Fas signaling mediated by the administration of recombinant FasL protein or an anti-Fas agonistic antibody causes acute lung inflammation [7?]. These findings suggested that the activation of FasL/Fas signaling in the lung is associated with the severity of the illness in lethal influenza virus infection. Type-I interferon is known as an anti-viral cytokine, which induces the expression of several intracellular proteins including OAS, RNase L and Mx proteins resulting in the reduction of virusImportance of Type I IFN and FasL in Influenzaproduction [10]. Production of type-I IFN is regulated by receptor proteins directly recognizing virus RNA, such as Toll like receptors (TLRs) and retinoic ac.I) the retention of anti-tumor cytotoxicity of the genetically engineered cells at concentrations of temozolomide that upregulate tumor associated stress molecules that activate effector cell functions. Intra-cavity post-resection administration of gliomareactive genetically engineered cd T cells presents one of the few opportunities to deliver concentrated cellular immunotherapy directly to the site of residual malignancy at the time of maximal tumor vulnerability during high dose chemotherapy. The in vitro effectiveness of our cd T cell-based DRI strategy provides thenecessary foundation to pursue such an innovative approach to the treatment of high-grade gliomas.AcknowledgmentsWe would like to thank Arthur Nienhuis (St. Jude University, Memphis, TN) for the SIV vector system.Author ContributionsConceived and designed the experiments: LSL GYG HTS. Performed the experiments: JB AD YS AJ. Analyzed the data: LSL AD HTS. Contributed reagents/materials/analysis tools: LSL GYG HTS. Wrote the paper: LSL AD HTS.
Influenza A virus infection causes acute respiratory inflammation and leads to lethal diseases including hyper lung pneumonia. It is known that influenza A viruses initially infect air-way epithelial cells and induce hyper production of several cytokines or chemokines. These cellular products induce anti-viral effects including direct inhibition of viral replication or recruitment and activation of several immune cells, such as macrophages, neutrophils or lymphocytes to eliminate the viruses or virusinfected cells [1]. FasL is a specific ligand of Fas, which is a type-I trans-membrane protein to induce cell death [2]. Functional mutation of the FasL or Fas gene causes abnormal proliferation of peripheral lymphocytes [3]. In immunological events, it is proposed that FasL protein expressed on killer T or natural killer cells plays a role in effector function for eliminating virus-infected cells and at a late phase after the infection, FasL/Fas signaling is essential for the suicide mechanism for activated peripheral lymphocytes to terminate inflammation [2]. Recently, it has beenshown by DNA microarray analysis using mice infected with the highly pathogenic H1N1 influenza A virus (r1918 strain) comparing with the non-lethal virus (T691 strain) that induction of the expression of FasL/Fas signal related genes in the lung is associated with the mortality of mammalians after the infection [4]. It is also reported that influenza A virus infection induces cell death of the infected cells by Fas-dependent apoptosis [5]. More importantly, it has been demonstrated that FasL gene functionally mutated congenic B6Smn.C3-Tnfsf6gld/J mice are more resistant to lethal influenza virus infection than C57Bl/6J mice [6]. Other studies demonstrated that activation of Fas signaling mediated by the administration of recombinant FasL protein or an anti-Fas agonistic antibody causes acute lung inflammation [7?]. These findings suggested that the activation of FasL/Fas signaling in the lung is associated with the severity of the illness in lethal influenza virus infection. Type-I interferon is known as an anti-viral cytokine, which induces the expression of several intracellular proteins including OAS, RNase L and Mx proteins resulting in the reduction of virusImportance of Type I IFN and FasL in Influenzaproduction [10]. Production of type-I IFN is regulated by receptor proteins directly recognizing virus RNA, such as Toll like receptors (TLRs) and retinoic ac.