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Eczema‐prone CCR4 −/− FoxP3 − bone marrow chimeras display defective immune responses following skin infection with vaccinia
Author(s) -
Freyschmidt EvaJasmin,
Mathias Clinton,
Caplan Benjamin,
Laouar Amale,
Swamy Manjunath N.,
Campbell James,
Wurbel MarcAndre,
Chatila Talal,
Oettgen Hans
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.490
Subject(s) - foxp3 , immunology , ccr4 , cd8 , vaccinia , biology , inflammation , bone marrow , cytotoxic t cell , immune system , virology , chemokine , chemokine receptor , genetics , gene , in vitro , recombinant dna
Eczema vaccinatum (EV) is a potentially lethal reaction to the small pox vaccine, vaccinia virus (VV), in atopic dermatitis (AD) patients. In order to establish a murine model of EV and to examine its immunological basis we VV‐infected mice displaying an AD‐like phenotype via skin scarification. Since the lack of FoxP3 + regulatory T cells in humans (IPEX syndrome) and in mice results in allergic inflammation, including AD, we choose FoxP3 − mice as a murine AD‐model. To confine the allergic inflammation to the skin, we further generated CCR4 −/− FoxP3 − bone marrow (BM) chimeras in which only cells derived from FoxP3 − mice are capable of CCR4 expression and hence of skin homing. We detected contiguous spread of virus from the inoculation site and appearance of new distant lesions, reminiscent of EV, as well as high viral loads in other organs in FoxP3 − mice and CCR4 −/− FoxP3 − BM chimeras. Consistent with this we found that viral specific CD8 + effector T cell responses were absent in FoxP3 − mice and significantly reduced in CCR4 −/− FoxP3 − BM chimeras. In contrast, intraperitoneal VV‐infection of CCR4 −/− FoxP3 − BM chimeras induced viral specific CD8 + effector T cell responses comparable to controls. We conclude that CD8 + effector responses are impaired when the virus is introduced via inflamed skin. This project has been funded in whole or in part from the NIAID, NIH (HHSN266200400030C, ADVN) and by a DFG research grant FR 2116/1‐1 to EJF.