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The Role of Intercellular Adhesion Molecule-1/LFA-1 Interactions in the Generation of Tumor-Specific CD8⁺ T Cell Responses¹

Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, United Kingdom

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.

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