Regulation of T cell-dependent autoantibody production by a γδ T cell line derived from lupus-prone mice

Lupus-prone (MRL×C57BL/6) F1 mice lacking γδ T cells show more severe lupus than their T cell-intact counterparts, suggesting that γδ T cells down-modulate murine lupus. To determine the mechanisms for this effect, we assessed the capacity of γδ T cell lines derived from spleens of αβ T cell-deficient MRL/Mp-Faslpr (MRL/Faslpr) mice to down-regulate anti-dsDNA production generated by CD4+αβ T helper cell lines and activated B cells from wild-type MRL/Faslpr mice. One line, GD12 (gd TCR+, CD4− CD8−), had the capacity to reduce anti-dsDNA production in a contact-dependent manner. GD12 also killed activated MRL/Faslpr (H-2k) B cells, with less cytolysis of resting B cells than that generated by in comparison to cytokine-matched γδ T cell lines. In addition, GD12 also killed activated B cells derived from C57BL/6-Faslpr (H-2b) or β2-microglobulin (β2 M)-deficient MRL/Faslpr mice, suggesting cytolysis was neither MHC- nor CD1-restricted. Killing by GD12 was inhibited by anti-TNFα and anti-TNF-R1, and partially blocked by anti-gd TCR Fab fragments, but not by anti-FasL, anti-TNF-R2 (p75) or concanamycin A. IL-10 produced by GD12 also partially inhibited αβ Th1-dependent but not αβ Th2-dependent autoantibody production. These findings prove that we have identtified a γδ T cell line that suppresses autoantibody synthesis by αβ T-B cell collaboration in vitro.