Selective Expression of the Chemokine Receptor XCR1 on Cross-presenting Dendritic Cells Determines Cooperation with CD8+ T Cells

Abstract

The expression of the chemokine receptor XCR1 and the function of its ligand XCL1 (otherwise referred to as ATAC, lymphotactin, or SCM-1) remained elusive to date. In the present report we demonstrated that XCR1 is exclusively expressed on murine CD8(+) dendritic cells (DCs) and showed that XCL1 is a potent and highly specific chemoattractant for this DC subset. CD8(+) T cells abundantly secreted XCL1 8-36 hr after antigen recognition on CD8(+) DCs in vivo, in a period in which stable T cell-DC interactions are known to occur. Functionally, XCL1 increased the pool of antigen-specific CD8(+) T cells and their capacity to secrete IFN-gamma. Absence of XCL1 impaired the development of cytotoxicity to antigens cross-presented by CD8(+) DCs. The XCL1-XCR1 axis thus emerges as an integral component in the development of efficient cytotoxic immunity in vivo.

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

“…However, it has recently been shown that the CD8 1 cDCs in mouse and the BDCA3 1 cDCs in human blood uniquely express XCR1. 21,31,32 The cultured CLEC9A 1 DC also expressed this molecule (Figure 1d). CLEC9A is therefore unique to spleen and blood CD141 1 DCs 16,24 and was thus used as a marker to distinguish this subset in subsequent experiments.…”

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

“…Based on the transcriptomic [33], functional [30,34] and developmental [35] [31,33]. Both subsets selectively express the membrane markers CADM1 [36], CLEC9A [37][38][39] and XCR1 [33,40,41] but are negative for SIRPa. Interestingly, XCL1, the chemokine ligand for XCR1 is selectively expressed by both activated NK and CD8 1 T cells [42] and Xcl1 mRNA is stored in central memory CD8 1 T lymphocytes [41].…”

“…Interestingly, XCL1, the chemokine ligand for XCR1 is selectively expressed by both activated NK and CD8 1 T cells [42] and Xcl1 mRNA is stored in central memory CD8 1 T lymphocytes [41]. Mice deficient for the XCL1-XCR1 chemotactic pathway develop significantly lower CD8 1 T-cell responses to vaccination with a model antigen [40] or early after infection with Listeria monocytogenes [41]. Hence, the specific expression of XCR1 on mouse CD8a 1 LT-DC and human BDCA3 1 DC likely contributes to their high ability for CD8 1 T-cell activation [40,41].…”

“…Mice deficient for the XCL1-XCR1 chemotactic pathway develop significantly lower CD8 1 T-cell responses to vaccination with a model antigen [40] or early after infection with Listeria monocytogenes [41]. Hence, the specific expression of XCR1 on mouse CD8a 1 LT-DC and human BDCA3 1 DC likely contributes to their high ability for CD8 1 T-cell activation [40,41]. Both human BDCA3 1 LT-DC and mouse CD8a 1 LT-DC express high levels of TLR3 and contain low to undetectable levels of the cytosolic RNA or DNA sensors RIG-I, MDA5 and DAI under steady-state conditions, [43,44].…”

The Lymphotactin Receptor Is Expressed in Epithelial Ovarian Carcinoma and Contributes to Cell Migration and Proliferation

“…XCL1 was first reported to attract CD4þ and CD8þ T lymphocytes and natural killer cells (16). Another study showed that XCR1 was expressed by murine CD8þ dendritic cells and their interaction with XCL1-positive CD8þ T cells regulated cytotoxic immunity (17,18). Furthermore, XCL1 induced migration of CD4þ and CD8þ T cells (19).…”