Human B7-H3 binds to Triggering receptor expressed on myeloid cells-like transcript 2 (TLT-2) and enhances T cell responses

Masaaki Hashiguchi, Yuka Inamochi, Shoya Nagai, Noriko Otsuki, Jinhua Piao, Hiroko Kobori, Yumiko Kanno, Hidefumi Kojima, Tetsuji Kobata, Miyuki Azuma

Department of Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

DOI: 10.4236/oji.2012.21002                

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.

Keywords

B7-H3; Co-Signal Molecule; T Cell; TLT-2

Conflicts of Interest

The authors declare no conflicts of interest.

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