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International Immunology Advance Access published online on October 3, 2007
International Immunology, doi:10.1093/intimm/dxm098
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Abrogation of CCL21 chemokine function by transgenic over-expression impairs T cell immunity to local infections

Heike Unsoeld1, Katja Mueller1, Ulrike Schleicher2, Christian Bogdan2, Jörg Zwirner3, David Voehringer4 and Hanspeter Pircher1

1 Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany
2 Department of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany
3 Department of Immunology, University of Göttingen, Göttingen, Germany
4 Institute for Immunology, Ludwig Maximilian University, Munich, Germany

Correspondence to: Correspondence to: H. Pircher; E-mail: hanspeter.pircher{at}uniklinik-freiburg.de

The CC chemokine receptor 7 (CCR7) and its two ligands, CCL21 and CCL19, play an important role in migration of immune cells to lymphoid tissue. To analyze the function of CCR7 in T cell immunity to infectious agents in vivo, transgenic (tg) mice expressing CCL21 in an ubiquitous fashion were generated. These mice contained high amounts of CCL21 in the serum (~0.3 µg/ml that resulted in CCR7 down-regulation and in a strongly impaired migration of T cells toward CCL21 in vitro. Lymph nodes in CCL21-tg mice were reduced in size but with intact microanatomy and normal distribution of T and B cells. CCL21-tg mice showed a significantly decreased CD8 T cell response to lymphocytic choriomeningitis virus after footpad infection, whereas the response after systemic infection was not altered. Likewise, the CD4 T cell response to footpad infection with Leishmania major was considerably lowered and CCL21-tg mice failed to clear parasites from infected skin. Taken together, these data demonstrate the importance of CCR7 in mediating T cell immunity to viral and parasitic pathogens after local infection.

Keywords: cell trafficking, in vivo desensitization, transgenic mice

Transmitting editor: Dr. H. Robson Mac Donald

Received 19 April 2007, accepted 10 August 2007.


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