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

Abstract
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 ( approximately 0.3 microg/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.
AuthorsHeike Unsoeld, Katja Mueller, Ulrike Schleicher, Christian Bogdan, Jörg Zwirner, David Voehringer, Hanspeter Pircher
JournalInternational immunology (Int Immunol) Vol. 19 Issue 11 Pg. 1281-9 (Nov 2007) ISSN: 0953-8178 [Print] England
PMID17914120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemokine CCL21
  • Receptors, CCR7
Topics
  • Animals
  • Arenaviridae Infections (immunology)
  • CD4-Positive T-Lymphocytes (immunology, metabolism)
  • CD8-Positive T-Lymphocytes (immunology, metabolism)
  • Chemokine CCL21 (blood, genetics, immunology)
  • Leishmania major (immunology)
  • Leishmaniasis, Cutaneous (immunology)
  • Lymph Nodes (cytology, immunology, metabolism)
  • Lymphocytic choriomeningitis virus (immunology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR7 (immunology, metabolism)
  • T-Lymphocytes (immunology)

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