Cutting edge: DNAX accessory molecule 1-deficient CD8+ T cells display immunological synapse defects that impair antitumor immunity

• Published in: The Journal of immunology (1950) 2014-01, Vol.192 (2), p.553-557
• Main Authors: Ramsbottom, Kelly M, Hawkins, Edwin D, Shimoni, Raz, McGrath, Mairi, Chan, Christopher J, Russell, Sarah M, Smyth, Mark J, Oliaro, Jane
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Differentiation, T-Lymphocyte - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; Cell Proliferation; Immunological Synapses - genetics; Immunological Synapses - immunology; Immunological Synapses - metabolism; Lipids - genetics; Lipids - immunology; Lymphocyte Function-Associated Antigen-1 - genetics; Lymphocyte Function-Associated Antigen-1 - immunology; Lymphocyte Function-Associated Antigen-1 - metabolism; Mice; Mice, Inbred C57BL
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302197

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.