αβ T Cell Regulation and CD40 Ligand Dependence in Murine Systemic Autoimmunity

Stanford L. Peng, Jennifer Madison McNiff, Michael P. Madaio, Jian Ma, Michael J. Owen, Richard A. Flavell, Adrian C. Hayday, Joe Craft

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

To explore the mechanisms by which αβ T cells and γδ T cells regulate systemic autoimmunity, lupus-prone mice were rendered deficient in CD40 ligand and/or αβ T cells by intercrossing CD40L -/- and TCR-α -/- knockouts, generating CD40L-intact or -deficient (CD40L+ or CD40L-), αß T cell-intact or -deficient (αβ+ or αβ-) MRL-lpr/lpr animals. As expected, CD40L+αβ+ mice developed high titer autoantibodies along with severe renal and cutaneous disease. CD40L+αβ- animals developed lower levels of autoantibodies, accompanied by less severe or delayed renal and cutaneous disease. CD40L-αβ+ mice developed even lower titers of autoantibodies and less severe renal disease yet developed cutaneous lesions indistinguishable from those of CD40L+αβ+ disease. Most surprisingly, CD40L-αβ- animals developed higher levels of some autoantibodies than did CD40L-αβ+ mice and developed renal disease similar in severity to CD40L+αβ- counterparts; however, they failed to develop skin disease. Thus, disruption of CD40L and αβ T cells provides a novel dissection of the physiology and pathology of murine lupus; while these data confirm previous findings demonstrating a role for CD40L-dependent, αβ T cell-dependent mechanisms in autoantibody production and renal disease in murine lupus, they also: 1) establish that αβ T cells may drive autoimmune skin disease by a CD40L-independent mechanism; 2) identify a role for CD40L in non-αβ T cell-dependent autoantibody production and autoimmune skin disease; and 3) suggest a role for αβ T cells in the down-regulation of autoimmunity driven by other T cells. Thus, both αβ and non-αβ T cells, such as γδ T cells, regulate systemic autoimmunity by CD40L-dependent and -independent mechanisms.

Original languageEnglish (US)
Pages (from-to)2464-2470
Number of pages7
JournalJournal of Immunology
Volume158
Issue number5
StatePublished - Mar 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Peng, S. L., McNiff, J. M., Madaio, M. P., Ma, J., Owen, M. J., Flavell, R. A., Hayday, A. C., & Craft, J. (1997). αβ T Cell Regulation and CD40 Ligand Dependence in Murine Systemic Autoimmunity. Journal of Immunology, 158(5), 2464-2470.