TITLE:
Human B7-H3 binds to Triggering receptor expressed on myeloid cells-like transcript 2 (TLT-2) and enhances T cell responses
AUTHORS:
Masaaki Hashiguchi, Yuka Inamochi, Shoya Nagai, Noriko Otsuki, Jinhua Piao, Hiroko Kobori, Yumiko Kanno, Hidefumi Kojima, Tetsuji Kobata, Miyuki Azuma
KEYWORDS:
B7-H3; Co-Signal Molecule; T Cell; TLT-2
JOURNAL NAME:
Open Journal of Immunology,
Vol.2 No.1,
March
19,
2012
ABSTRACT: The B7 family member B7-H3 is broadly expressed in many tissue and tumor types. B7-H3 expression is induced on some immune cells; however, its immunological function remains controversial, because both immunoenhancing and immunoinhibitory effects have been reported in human and mouse systems. We have previously reported the following: 1) murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2), a member of the TREM family of receptors; and 2) the B7-H3:TLT-2 pathway up-regulated T cell responses. However, the expression and function of human TLT-2 has not yet been clarified. A recent study found no evidence to support the existence of an interacttion between human B7-H3 and TLT-2. In this study, we demonstrated that human B7-H3 binds to TLT-2 and augments T cell responses. Human and mouse B7-H3Ig chimeric proteins cross-interacted with both human and mouse species of TLT-2-transduced cells. Human TLT-2 was expressed on freshly isolated, peripheral blood B cells and monocytes, and subpopulations of CD4+ and CD8+ T cells. Human TLT-2 expression on T cells did not correlate with na?ve or memory phenotypes and was diminished after culture, despite the presence of mitogenic stimuli. Constitutive TLT-2 expression on monocytes was also down-regulated after culture. Human B7-H3 transfectants augment IL-2 production from TLT-2-transduced T cell hybridomas, and IFN-γ production from peripheral blood CD4+ and CD8+ T cells. The enhanced responses were inhibited by the addition of anti-TLT-2 mAbs, suggesting TLT-2-mediated costimulatory effect. Our results demonstrate the existence of a functional interaction between human B7-H3 and TLT-2, and the restricted expression of TLT-2 on T cells and monocytes.