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 language||English (US)|
|Number of pages||7|
|Journal||Journal of Immunology|
|State||Published - Mar 1 1997|
ASJC Scopus subject areas
- Immunology and Allergy