The role of intercellular adhesion molecule-1/LFA-1 interactions in the generation of tumor-specific CD8+ T cell responses.
The activation of naive CD4+ T cells requires both TCR engagement and a second costimulatory signal mediated by the interaction of CD28 with CD80/CD86 expressed on professional APC. However, the situation for naive CD8+ T cells is less clear. Although evidence indicates that induction of CD8+ T cell responses is also dependent on professional APC, the ability of some tumors, which do not express CD80/CD86, to induce CTL suggests that other pathways of costimulation exist for the activation of CD8+ T cells. We examined the ability of tumor cells expressing different levels of a tumor-specific Ag to directly prime CD8+ T cells. We demonstrate that CD8+ T cells are directly activated by tumor cells in a CD80/CD86-CD28 independent manner. In this system, costimulation requires ICAM-1/LFA-1 interaction. This results in the generation of CTL capable of inhibiting tumor growth in vivo, and maintaining long-term survival.
Jenkinson
S Rhiannon
SR
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
Williams
Neil A
NA
Morgan
David J
DJ
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1