Trem-Like Transcript 2 Is Expressed on Cells of the Myeloid/Granuloid and B Lymphoid Lineage and Is Up-Regulated in Response to Inflammation

Abstract

The triggering receptor expressed on myeloid cells (TREM) gene cluster encodes a group of transmembrane proteins that are emerging as important components in innate and adaptive immunity. In both mice and humans, the TREM gene cluster encodes eight receptors; only four of these, however, are direct homologs: TREM-1, TREM-2, TREM-like transcript 1 (TLT1), and TLT2. Of the transmembrane receptors encoded by the four conserved genes within this cluster, TLT2 has not been studied previously. Data presented in this study demonstrate that TLT2 is expressed early in B cell development in conjunction with B220 and is detected on all developing mouse B cell populations as well as B cells in the periphery. TLT2 expression on B cells in the periphery exhibits a distinct hierarchy with the highest detectable levels observed on B1 B cells in the peritoneum. The overall gradation of TLT2 expression on B cells is: B1 > marginal zone/transitional 2 > transitional 1 > follicular. Additionally, TLT2 expression was observed on mouse neutrophils throughout the body. Although monocytes were not observed to express TLT2, resident peritoneal and lung macrophages do express TLT2, suggesting that it is up-regulated in association with terminal differentiation of monocytes. Finally, both neutrophils and macrophages were observed to up-regulate TLT2 expression in vivo in response to inflammatory stimuli, whereas TLT2 expression on B cells remained unchanged. In conclusion, the data suggest that TLT2 may be involved in the innate immune response based on its expression profile and the fact that it is up-regulated in response to inflammation.

Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses

“…Although research on TREM proteins has focused on myeloid lineage cells, in the present study, we highlight the expression and function of TREM family members in T cells. Consistent with a previous report (27), TLT-2 was expressed predominantly on B cells and macrophages, although we observed significant expression on freshly isolated unstimulated CD8 ϩ T cells and activated CD4 ϩ and CD8 ϩ T cells after short-term stimulation. The augmentation of proliferation and cytokine production costimulated with B7-H3-transfectants were consistently observed in both types of T cells that expressed endogenous TLT-2 and exogenously introduced high levels of TLT-2 ( Figs.…”

“…Although the above results were obtained by staining with MIH47, staining by using MIH49 showed higher levels of TLT-2 expression on B cells ( Fig. S1C) and myeloid cells (data not shown), which was consistent with results presented in a previous report (27). Differential reactivities of these mAbs may be because of differences in epitopes on TLT-2 and glycosylation in respective cell types.…”

Functional Analysis of Activating Receptor LMIR4 as a Counterpart of Inhibitory Receptor LMIR3

“…For example, TLT2 expression on monocytes is up-regulated by in vivo administration of LPS (53). As both LMIR3 and LMIR4 are expressed predominantly in myeloid cells, the possibility arose that the expression levels of these receptors are regulated by inflammation.…”

The contrasting role of B7-H3

“…TLT-2 is constitutively expressed on CD8 T cells, B cells, NK cells, macrophages, DC, and neutrophils, and is induced on activated CD4 T cells. Unlike other members of the TREM family, TLT-2 is not associated with DAP12 for signaling, but contains a potential SH3-binding motif and an endocytosis motif in the cytoplasmic tail (5,6). The downstream mechanism mediated by the B7-H3/TLT-2 pathway remains elusive.…”