Human TLT2 is expressed on and potentiates chemotaxis of cells of both myeloid and lymphoid lineage (158.6)

Abstract

Abstract The TREM locus encodes a family of innate immune receptors, which play diverse roles in modulating the immune response. Trem-like transcript 2, or TLT2, is the only family member expressed on both myeloid and lymphoid cells, and is conserved among mouse and man, with 60% sequence homology between murine (m) and human (h) TLT2. Previous work by our lab defined the expression pattern for mTLT2 on cells of the immune system: granulocytes, macrophages, and B cells all express mTLT2, whereas monocytes and T cells do not. When mTLT2 is ligated with αTLT2 1C5 mAb, neutrophil chemotaxis is enhanced in a dose dependent manner in response to chemokines. To further understand the biological function of TLT2, our lab has characterized hTLT2 expression on peripheral leukocytes and studied its role in potentiating chemotaxis. Human granulocytes, monocytes, macrophages, NK cells, and B cells all express hTLT2 on their surface. Furthermore, interaction with antigen and differentiation downregulates surface expression of hTLT2 on B cells. In contrast, activation of granulocytes or monocytes with PMA upregulates hTLT2 expression. Lastly, naive, memory, and in vitro activated T cells do not express hTLT2, opposed to results from other groups. Functionally, ligation of hTLT2 augments B cell chemotaxis towards CXCL13, and neutrophil migration towards IL-8. In this regard, we observe hTLT2 and mTLT2 to have conserved phenotypic expression and function throughout the immune compartment.