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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 270985, 11 pages
http://dx.doi.org/10.1155/2010/270985
Research Article

Autocrine, Not Paracrine, Interferon-Gamma Gene Delivery Enhances Ex Vivo Antigen-Specific Cytotoxic T Lymphocyte Stimulation and Killing

1Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2Research and Therapy Center for Hepatic Diseases, The 2nd Affiliated Hospital, The 2nd Medical College, Chongqing Medical University, Chongqing 630046, China
3Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
4Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
5Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USA

Received 30 November 2009; Accepted 24 February 2010

Academic Editor: Hanchun Yang

Copyright © 2010 Dazhi Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTL) shows promise in the treatment of cancer and infectious diseases. We utilize adeno-associated virus-(AAV-) based antigen gene-loaded dendritic cells (DCs) to stimulate such antigen-specific CTL. Yet further improvements in CTL stimulation and killing may result by gene delivery of various Th1-response interferons/cytokines, such as interferon (IFN- ), as the delivered gene can continuously produce that interferon. However which immune cell type should optimally express IFN- is unclear as the phenotypes of both DC and T cells are enhanced by it. Here, we used AAV to compare and contrast IFN- gene delivery into DC or T cells, and versus the addition of exogenous IFN- , for stimulating carcinoembryonic antigen-(CEA-) specific CTL. It was found that AAV/IFN- delivery into T cells (autocrine) resulted in T cell populations with the highest CD8(+)/CD4(+) ratio, highest IFN- (+)/IL-4(+) ratio, highest CD69(+),CD8(+) levels, and lowest CD4(+)/CD25(+) levels, all consistent with the strongest Th1 response. Most importantly, AAV/IFN- transduction of T cells resulted in antigen-specific T cell populations with the highest killing capabilities, 49% above other treatments. These data strongly suggest that AAV/IFN- autocrine gene delivery into T cells is worthy of further study towards maximizing the generation of antigen-specific anticancer CTL killers.