HSV type 1 Infected Cell Extract

We investigated the influence of a transient treatment of corticosteroid on CD8(+) T cells during herpesvirus infection. Dexamethasone, a synthetic corticosteroid, induced apoptosis of naive and memory CD8(+) T cells but virus-specific effector cells were spared. CD8(+) T cell susceptibility was directly correlated with the expression of nr3c1. Both alpha-(HSV1) and gamma-(MHV68) herpesvirus infection expanded CD8(+) T cells down regulated nr3c1 indicating corticosteroid-mediated effects were not limited to one pathogen or the specific clonotype. Dexamethasone compromised anti-viral immunity to subsequent infections, likely through reductions in the naive cell pool. Dexamethasone augmented the function and inflammatory tissue homing potential of effector cells via upregulation of CXCR3. Accordingly, an antibody neutralization of CXCR3 diminished dexamethasone-induced migration of CD8(+) T cells to tissues resulting in increased virus burden. Our study therefore suggests that even a transient corticosteroid therapy influences both ongoing CD8(+) T cell responses as well as the size of the naive and memory repertoire.

The use of a novel therapeutic vector containing HSV1-thymidine kinase (HSV1-tk) and a short hairpin RNA for the MDR1 gene (shMDR) was proposed previously. We investigated the antitumor effects in an in vivo mouse model of colon cancer and assessed treatment response by serial non-invasive imaging. shMDR-TK expressing (MTKG) tumors for the dual therapy group mice with ganciclovir and doxorubicin showed a decrease in size, while tumors in the single therapy group mice showed a moderate increase (p < 0.05). The I-131-5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) uptake ratio of MTKG-to-parent HCT-15 tumors decreased as treatment progressed for single or dual therapy group mice, while that of the control group mice increased gradually. This study demonstrates the enhanced antitumor effects with combination gene therapy compared with a single therapeutic approach, and provides the potential of therapeutic response monitoring. (C) 2009 Elsevier Ireland Ltd. All rights reserved.