The development of CIA is suppressed in Cxcr4flox/flox/ Lck-Cre mice. (a) Targeting strategy for the generation of conditional knockout mice of Cxcr4. T cell-specific Cxcr4-targeted (Cxcr4flox/flox/Lck-Cre) mice were generated as described in Materials and methods. (b) Incidence of CIA. (c) Severity of CIA. Mice were immunized with chicken IIC emulsified with CFA intradermally at triple sites into the back on day 0 and 21. Open circles, Cxcr4+/+ mice (n = 6); open diamonds, Cxcr4flox/flox mice (n = 6); open triangles, Cxcr4+/+/Lck-Cre mice (n = 9); solid circles, Cxcr4flox/flox/Lck-Cre mice (n = 11). Representative data obtained from two independent experiments are shown. Averages and SDs are indicated in c. **p < 0.01; Cxcr4flox/flox/Lck-Cre mice versus Cxcr4+/+ and Cxcr4flox/flox mice. *p < 0.05; Cxcr4flox/flox/Lck-Cre mice versus Cxcr4+/+/Lck-Cre mice, by χ2-test. (d)Histologic changes of the joints after induction of CIA. After the inspection of the arthritis development shown in b and c, hindlimbs were removed at 60 days after the first immunization, and paraffin sections of joints were stained with hematoxylin and eosin. The histology of the joint of a IIC-immunized and arthritis-developed Cxcr4+/+/Lck-Cre mouse (Cxcr4+/+/Lck-Cre, developed) shows severe erosion of the bone (arrows) and hyperplasia of synovial membrane (*), whereas no such abnormalities are seen in the joints of Cxcr4flox/flox/Lck-Cre mice that did not develop arthritis (Cxcr4flox/flox/Lck-Cre, not developed). A Cxcr4flox/flox/Lck-Cre mouse that developed arthritis (Cxcr4flox/flox/Lck-Cre, developed) shows severe bone erosion (arrows) and pannus-like structure (*), comparable to those of control mice. × 40. Typical histologies are shown in 22 representative sections from three mice for each group.