Cutting Edge: DNAX Accessory Molecule 1–Deficient CD8+ T Cells Display Immunological Synapse Defects That Impair Antitumor Immunity

Cutting Edge: DNAX Accessory Molecule 1–Deficient CD8+ T Cells Display Immunological Synapse Defects That Impair Antitumor Immunity

The Journal of Immunology, January 2014

24337740

Kelly M. Ramsbottom, Edwin D. Hawkins, Raz Shimoni, Mairi McGrath, Christopher J. Chan, Sarah M. Russell, Mark J. Smyth, Jane Oliaro

DNAX accessory molecule 1 (DNAM-1) is expressed on all CD8(+) T cells and promotes their activation and effector function. DNAM-1 interacts with LFA-1, a critical molecule for immunological synapse formation between T cells and APCs, and for cytotoxic killing of target cells. Mice that lack DNAM-1 display abnormal T cell responses and antitumor activity; however, the mechanism involved is unclear. In this article, we show that DNAM-1 deficiency results in reduced proliferation of CD8(+) T cells after Ag presentation and impaired cytotoxic activity. We also demonstrate that DNAM-1-deficient T cells show reduced conjugations with tumor cells and decreased recruitment of both LFA-1 and lipid rafts to the immunological synapse, which correlates with reduced tumor cell killing in vitro. This synapse defect may explain why DNAM-1-deficient mice cannot clear tumors in vivo, and highlights the importance of DNAM-1 and the immunological synapse in T cell-mediated antitumor immunity.