Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus

Citation
Bl. Liang et al., Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus, J IMMUNOL, 165(6), 2000, pp. 3436-3443
Citations number
43
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
6
Year of publication
2000
Pages
3436 - 3443
Database
ISI
SICI code
0022-1767(20000915)165:6<3436:ARAPRB>2.0.ZU;2-0
Abstract
The activation of T lymphocytes requires both Ag-mediated signaling through the TCR as well as costimulatory signals transmitted through B7-1 and/or B 7-2 with CD28, The interference of B7-mediated costimulatory signals has be en proposed as one immunotherapeutic intervention for the prevention autoim mune disease. This study has examined autoantibody responses and autoimmune pathology in a murine model of human systemic lupus erythematosus (SLE), t he MRL-lpr/lpr mouse, genetically deficient in B7-1 or B7-2, or in mice tre ated with B7-1/B7-2 blocking Abs, In contrast to other studies of murine mo dels of SLE, MRL-lpr/lpr mice treated with B7 blocking Abs exhibit strong a nti-small nuclear ribonucleoprotein (snRNP) and anti-DNA autoantibody respo nses with some changes in isotype switching as compared with untreated anim als. All MRL-lpr/lpr mice deficient in B7-1 or B7-2 produce anti-snRNP and anti-DNA titers with isotypes virtually identical with wild-type animals. H owever, the absence of B7-2 costimulation did interfere with the spontaneou s activation and the accumulation of memory CD4(+) or CD8(+) T lymphocytes characteristic of wild-type MRL-lpr/lpr mice, IgG and C3 complement deposit ion was less pronounced in the kidneys of B7-2 deficient MRL-lpr/lpr mice, reflecting their lessor degree of glomerulonephritis. By comparison, B7-1-d eficient MRL-lpr/lpr mice had more severe IgG and C3 deposits in glomeruli.