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Published online before print February 9, 2005
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*Department of Hematology and Oncology, Graduate School of Medicine, and Graduate School of Biostudies and Institute for Virus Research, Kyoto University, Japan; and Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
@ To whom correspondence should be addressed. E-mail: kadowaki{at}kuhp.kyoto-u.ac.jp.
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Abstract |
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Dendritic cells (DCs) coordinate T cell responses by producing T cell-attracting chemokines and by inducing the expression of chemokine receptors on T cells. Scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) is a unique chemokine that also functions as an endocytic receptor and an adhesion molecule in its membrane-bound form. SR-PSOX/CXCL16 is the only known ligand of CXC chemokine receptor 6 (CXCR6) that is expressed on activated T cells and thus, may play an important role in enhancing effector functions of T cells. Here, we investigated the expression of SR-PSOX/CXCL16 on human DC subsets and that of CXCR6 on T cell subpopulations to elucidate the dynamics of CXCL16/CXCR6 interaction in DC/T cell responses. Membrane-bound SR-PSOX/CXCL16 was expressed on macrophages, monocyte-derived DCs, and blood myeloid DCs, and the expression increased after DC maturation. Myeloid antigen-presenting cells constitutively secreted SR-PSOX/CXCL16 for an extended period, suggesting the involvement of CXCL16 in peripheral and lymphoid tissues. Plasmacytoid DCs hardly expressed SR-PSOX/CXCL16 on their surfaces but secreted significant amounts of SR-PSOX/CXCL16. A subset of CD4+ effector memory T (TEM) cells constitutively expressed CXCR6, whereas central memory T cells (TCM) and naïve T cells did not. Upon stimulation with mature DCs, however, the expression of CXCR6 on TCM cells was markedly up-regulated, whereas the expression on naïve T cells was induced only weakly. These results suggest that the interaction between SR-PSOX/CXCL16 and CXCR6 plays an important role in enhancing TCM cell responses by mature DCs in lymphoid tissues and in augmenting TEM cell responses by macrophages in peripheral inflamed tissues.
Key Words: antigen-presenting cells • chemokine • chemokine receptor
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