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

First Author  Sireci G Year  2007
Journal  Eur J Immunol Volume  37
Issue  2 Pages  425-33
PubMed ID  17273990 Mgi Jnum  J:117903
Mgi Id  MGI:3697970 Doi  10.1002/eji.200636695
Citation  Sireci G, et al. (2007) Immunoregulatory role of Jalpha281 T cells in aged mice developing lupus-like nephritis. Eur J Immunol 37(2):425-33
abstractText  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 Valpha14Jalpha281 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 IgG(3 )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 IgG(3), 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.
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