IFN-gamma-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-gamma.
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.
Beatty
G
G
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Paterson
Y
Y
D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured / Q000637:transplantation
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D007371:Interferon-gamma