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Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis.

Abstract：

:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the emergence of autoreactive T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted invariant natural killer T (iNKT) cells, suggesting a key role for these cells in its immunopathogenesis. This subset uses an invariant TCR constituted by Valpha14 Jalpha281 chains paired with some Vbeta domains. The regulatory role for iNKT cells in non-autoimmune mice was suggested by our previous results showing that aged Jalpha281 knockout (KO) mice produce anti-dsDNA. Here we show that old Jalpha281 KO mice have proteinuria and antibodies against dsDNA and cardiolipin. Histological analysis of Jalpha281 KO mice revealed glomeruli damage and deposition of C3c and IgG, mainly of the IgG3 subclass. In spleens of aged Jalpha281 KO mice there is an increase of activated marginal zone B cells. The evolution of lesions may depend on the age-associated increase of autoantibodies production, preferentially IgG3, mainly secreted by marginal zone B cells. Our results provide the first evidence of a lupus-like syndrome in non-autoimmune mice, supporting an age-related immunoregulatory role of Jalpha281+ cells, probably associated with the activation of marginal zone B cells.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Sireci G,Russo D,Dieli F,Porcelli SA,Taniguchi M,La Manna MP,Di Liberto D,Scarpa F,Salerno A

doi

10.1002/eji.200636695

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

425-33

issue

2

eissn

0014-2980

issn

1521-4141

journal_volume

37

pub_type

杂志文章

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