期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 112, 期 8, 页码 1211-1222出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI200317165
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资金
- NCI NIH HHS [R01 CA052511, CA-52511] Funding Source: Medline
- NIAID NIH HHS [N01AI40093] Funding Source: Medline
In vivo treatment of mice with the natural killer T (NKT) cell ligand, a.-galactosylceramide (alphaGalCer), ameliorates autoimmune diabetes and experimental autoimmune encephalomyelitis (EAE) by shifting pathogenic Th1-type immune responses to nonpathogenic Th2-type responses. In the current study, in vivo activation of NKT cells in adult NZB/W mice by multiple injections of alphaGalCer induced an abnormal Th1-type immune response as compared with the Th2-type response observed in nonautoimmune C57BL/6 mice. This resulted in decreased serum levels of IgE, increased levels of IgG2a and IgG2a anti-double-stranded DNA (anti-dsDNA) Ab's, and exacerbated lupus. Conversely, treatment of NZB/W mice with blocking anti-CD1d mAb augmented Th2-type responses, increased serum levels of IgE, decreased levels of IgG2a and IgG2a anti-dsDNA Ab's, and ameliorated lupus. While total CD4(+) T cells markedly augmented in vitro IgM anti-dsDNA Ab secretion by splenic B cells, the non-CD1d-reactive (CD1d-alphaGalCer tetramer-negative) CD4(+) T cells (accounting for 95% of all CD4(+) T cells) failed to augment Ab secretion. The CD1d-reactive tetramer-positive CD4(+) T cells augmented anti-dsDNA Ab secretion about tenfold. in conclusion, activation of NKT cells augments Th1-type immune responses and autoantibody secretion that contribute to lupus development in adult NZB/W mice, and anti-CD1d mAb might be useful for treating lupus.
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