Global T cell dysregulation in non-autoimmune-prone mice promotes rapid development of BAFF-independent, systemic lupus erythematosus-like autoimmunity

William Stohl, Noam Jacob, William J. Quinn, Michael P. Cancro, Huaxin Gao, Chaim Putterman, Xiaoni Gao, Luminita Pricop, Michael N. Koss

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

In otherwise non-autoimmune-prone C57BL/6 (B6) mice rendered genetically deficient in CD152 (CTLA-4), polyclonal hypergammaglobulinemia with increased levels of systemic lupus erythematosus (SLE)-associated IgG autoantibodies, glomerular IgG and C3 deposition, and interstitial nephritis all developed by 3-5 wk of age. Remarkably, superimposing genetic deficiency of BAFF (B cell-activating factor belonging to the TNF family) onto CD152 deficiency did not substantially attenuate humoral autoimmunity and immunopathology in these mice, despite the resulting marked reduction in B-lineage cells. Although superimposing a BAFF transgene (resulting in constitutive BAFF overexpression) onto CD152-deficient mice did lead to increases in B-lineage cells and serum levels of certain SLE-associated IgG autoantibodies, renal immunopathology remained largely unaffected. Taken together, these results demonstrate that global T cell dysregulation, even in an otherwise non-autoimmune-prone host, can promote systemic humoral autoimmunity and immunopathology in a BAFF-independent manner. Moreover, supraphysiologic expression of BAFF in the setting of ongoing autoimmunity does not necessarily lead to greater immunopathology. These findings may help explain the limited clinical efficacy appreciated to date of BAFF antagonists in human SLE.

Original languageEnglish (US)
Pages (from-to)833-841
Number of pages9
JournalJournal of Immunology
Volume181
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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