Distinct in vivo roles of CD80 and CD86 in the effector T-cell responses inducing antigen-induced arthritis.
CD80 and CD86 play a critical role in the initiation of T-cell responses. However, their role in the in vivo effector CD4+ T-cell responses has been less extensively investigated. The current studies have examined the functional relevance of CD80 and CD86 in the effector CD4+ T-cell responses inducing antigen-induced arthritis. Arthritis was induced in C57BL/6 mice by sensitization to methylated bovine serum albumin (mBSA) on day 0, booster immunization (day 7) and intra-articular injection of mBSA (day 21). Control or anti-CD80 and/or anti-CD86 monoclonal antibodies were administered from day 21 to day 28. Arthritis severity and immune responses were assessed on day 28. The development of arthritis was significantly suppressed by inhibition of CD80 or CD86. Blockade of both CD80 and CD86 caused a trend towards reduced disease severity compared to control antibody-treated mice. Neutralization of CD80 attenuated accumulation of CD4+ T cells in joints and enhanced splenocyte production and circulating levels of interleukin-4. Inhibition of CD86 or both CD80 and CD86 reduced T-cell accumulation in joints without affecting T helper type 1/type 2 (Th1/Th2) differentiation or antibody levels. Blockade of CD86, and not CD80, significantly suppressed splenocyte interleukin-17 (IL-17) production. These results provide further in vivo evidence that CD80 and CD86 play important pathogenic roles in effector T-cell responses. CD80 exacerbates arthritis by downregulating systemic levels of IL-4 and increasing T-cell accumulation in joints without affecting IL-17 production. CD86 enhances disease severity by upregulating IL-17 production and increasing the accumulation of effector T cells in joints without affecting Th1/Th2 development.
Odobasic
Dragana
D
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Monash Medical Centre, Clayton, Vic, Australia. dragana.odobasic@med.monash.edu.au
Leech
Michelle T
MT
Xue
Jin R
JR
Holdsworth
Stephen R
SR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D007074:Immunoglobulin G; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine