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.

journal_name

Int Immunol

journal_title

International immunology

authors

Unsoeld H,Mueller K,Schleicher U,Bogdan C,Zwirner J,Voehringer D,Pircher H

doi

10.1093/intimm/dxm098

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1281-9

issue

11

eissn

0953-8178

issn

1460-2377

pii

dxm098

journal_volume

19

pub_type

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