A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells.


Chemokine receptor CXCR3 and its CXC ligands play major roles in Th1 cell-induced inflammatory processes. Here, we examined the expression of CXCR3 by TCR-transgenic Th1 lymphocytes that induce ocular inflammation in mice expressing the target antigen in their lenses. The essential role of CXCR3 in this model was indicated by the observation that the ocular inflammation was significantly blocked by an antibody against this receptor. CXCR3 expression by Th1 cells was elevated during their initial activation in culture and further increased during the consecutive incubation with IL-2. However, CXCR3 expression declined dramatically during the ensuing antigenic reactivation, in parallel with down-regulation of its mRNA. Yet, reactivated Th1 cells exhibited the highest degree of pathogenicity when adoptively transferred into recipients. Transferred reactivated Th1 cells proliferated vigorously and re-expressed CXCR3 while residing in the spleen of recipient mice, reaching approximately 85% positivity 4 days post cell transfer when their massive migration to the target eyes began. Importantly, infiltrating Th1 cells underwent profound phenotypic changes in the eye that closely resembled those seen during reactivation of Th1 cells in vitro and included down-regulation of CXCR3. These observations thus show that expression of CXCR3, a major participant in Th1-induced inflammation, fluctuates profoundly during cell activation and migration and is down-regulated upon re-exposure of these cells to the antigen, in vitro or in the target organ.


Citations per Year

82 Citations

Semantic Scholar estimates that this publication has 82 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Chen2004AUP, title={A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells.}, author={Jun Chen and Barbara P. Vistica and Hiroshi Takase and Don Il Ham and Robert N. Fariss and Eric Wawrousek and Chi-chao Chan and Julie A Demartino and Joshua Farber and Igal Gery}, journal={European journal of immunology}, year={2004}, volume={34 10}, pages={2885-94} }