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The Journal of Immunology, 2001, 166: 2276-2282.
Copyright © 2001 by The American Association of Immunologists

IFN-{gamma}-Dependent Inhibition of Tumor Angiogenesis by Tumor-Infiltrating CD4+ T Cells Requires Tumor Responsiveness to IFN-{gamma}1

Gregory L. Beatty and Yvonne Paterson2

Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104

The importance of CD4+ T cells in the induction of an optimal antitumor immune response has largely been attributed to their ability to provide costimulatory signals for the priming of MHC class I-restricted CD8+ CTL. However, many reports have demonstrated a requirement for CD4+ T cells in the effector phase of tumor rejection indicating a greater responsibility for CD4+ T cells in controlling tumor outgrowth. We demonstrate here a critical role for CD4+ T cells in restraining initial tumor development through the inhibition of tumor angiogenesis. Using a tumor variant that is unresponsive to IFN-{gamma}, we show that tumor responsiveness to IFN-{gamma} is necessary for IFN-{gamma}-dependent inhibition of tumor angiogenesis by CD4+ T cells. These studies reveal a pivotal role for CD4+ T cells in controlling early tumor development through inhibition of tumor angiogenesis.




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