Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids

Abstract

We examined the in vivo behavior of liver natural killer T cells (NKT cells) by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6+ cells in liver, were found to crawl within hepatic sinusoids at 10–20 μm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance.

Immediate antigen‐specific effector functions byTCR‐transgenic CD8+ NKT cells

“…Similar to iNKT cells, the tgNKT cells are most abundant in the liver, where they are likely to interact, similar to iNKT cells, continuously with LSEC in a physiological fashion [52]. Antigen-specific interaction of tgNKT cells obtained from OT-I mice with LSEC cross-presenting ovalbumin lead to most efficient elimination of antigenpresenting cells in vitro and prevented the ability of LSEC to induce tolerance in naive transgenic CD8 T cells (Fig.…”

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

“…Such signaling in turn regulates thymic medullary chemokine secretion [17]. Establishment of iNKT cells tissue residency in the periphery requires expression of the Sphingosine1-Phosphate 1 receptor (S1P1R) by iNKT cells [18] and more specifically expression of CxCR6 for liver localization [19].…”

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

“…In mice, these T cells are predominantly invariant NKT (iNKT) cells expressing an invariant TCRab, formed by the Va14 chain paired with the Vb2, Vb7, or Vb8 chain. These cells patrol the murine liver sinusoids where they represent ∼20% of resident lymphocytes and can release proinflammatory cytokines (2,3). iNKT cells recognize glycolipid Ags presented by the nonpolymorphic CD1d molecule (4) and play an important role in the pathogenesis with different etiologies (5)(6)(7)(8).…”