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

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

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

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. Copyright ? 2014 by The American Association of Immunologists, Inc
Original languageEnglish
Pages (from-to)553 - 557
Number of pages5
JournalJournal of Immunology
Volume192
Issue number2
DOIs
Publication statusPublished - 2014

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