Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids (original) (raw)
Figure 6
Decreased Patrolling Efficiency and Decreased ConA Hepatitis Severity in CXCR6-Deficient Mice
(A) Serum transaminase levels in cxcr6gfp/gfp, cxcr6gfp/+, and cxcr6+/+ littermates 12 h after a challenge with 20 mg/kg ConA IP. Results are pooled from two independent experiments. The horizontal line represents the upper limit for normal serum transaminase levels, as measured in unchallenged mice. Asterisk indicates a two-tailed student's _t_-test with a p < 0.05 in comparison with littermates.
(B) Hematoxylin and eosin staining of paraffin-embedded liver sections from cxcr6gfp/+ and cxcr6gfp/gfp mice sacrificed 12 h after a challenge with 20 mg/kg ConA IP.
(C) Reduced sinusoid patrolling by NKT cells in cxcr6gfp/gfp mice. By measuring the average inter-nuclei distance of hepatocytes in high-magnification images, the average sinusoidal length of a hepatocyte was determined to be 28.6 μm (data not shown). Utilizing the lymphocyte velocity data (left panel) and assuming that a CD1d-reactive T cell can contact only one hepatocyte at a time, we calculated that each CD1d-reactive T cell can visit 0.58 hepatocytes/min in the cxcr6gfp/+ mice, and 0.64 hepatocytes/min in the CXCR6-deficient mice. The density of GFP+ cells in cxcr6gfp/+ and cxcr6gfp/gfp mice (middle panel) was calculated from the intravital videos used in Figure 3 and the flow cytometry data in Figure 2. Combining the similar crawling velocities with the different steady-state densities, we show decreased rate of patrolling by GFP+ lymphocytes, expressed as the average time between “visitation” of any single hepatocyte (right panel).