Regulation of T cell-dependent autoantibody production by a gammadelta T cell line derived from lupus-prone mice.
Lupus-prone (MRLxC57BL/6) F(1) mice lacking gammadelta T cells show more severe lupus than their T cell-intact counterparts, suggesting that gammadelta T cells down-modulate murine lupus. To determine the mechanisms for this effect, we assessed the capacity of gammadelta T cell lines derived from spleens of alphabeta T cell-deficient MRL/Mp-Fas(lpr) (MRL/Fas(lpr)) mice to down-regulate anti-dsDNA production generated by CD4(+)alphabeta T helper cell lines and activated B cells from wild-type MRL/Fas(lpr) 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/Fas(lpr) (H-2(k)) B cells, with less cytolysis of resting B cells than that generated by in comparison to cytokine-matched gammadelta T cell lines. In addition, GD12 also killed activated B cells derived from C57BL/6-Fas(lpr) (H-2(b)) or beta(2)-microglobulin (beta(2) M)-deficient MRL/Fas(lpr) mice, suggesting cytolysis was neither MHC- nor CD1-restricted. Killing by GD12 was inhibited by anti-TNFalpha 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 alphabeta Th1-dependent but not alphabeta Th2-dependent autoantibody production. These findings prove that we have identtified a gammadelta T cell line that suppresses autoantibody synthesis by alphabeta T-B cell collaboration in vitro.
Fujii
Takao
T
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA. takfujii@kuhp.kyoto-u.ac.jp
Okada
Masato
M
Craft
Joe
J
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000974:Antibodies, Antinuclear; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004247:DNA