Depletion of collagen II-reactive T cells and blocking of B cell activation prevents collagen II-induced arthritis in DBA/1j mice.
Collagen II (CII)-induced arthritis in DBA/1j mice is mediated by both CII-reactive T cells and anti-CII Ab-producing B cells. To determine the relative role of these processes in the development of arthritis, we specifically eliminated CII-reactive T cells by treating the mice with CII-pulsed syngeneic macrophages that had been transfected with a binary adenovirus system. These macrophages express murine Fas ligand in a doxycycline-inducible manner with autocrine suicide inhibited by concomitant expression of p35. The mice were treated i.v. with four doses of CII-APC-AdFasLp35Tet or a single dose of AdCMVsTACI (5 x 10(9) PFU), or both simultaneously, beginning 2 wk after priming with CII in CFA. Treatment with CII-APC-AdFasLp35Tet alone or in combination with a single dose of AdCMVsTACI prevented the development of CII-induced arthritis and T cell infiltration in the joint. The elimination of T cells was specific in that a normal T cell response was observed on stimulation with OVA after treatment with CII-APC-AdFasLp35Tet. Treatment with AdCMVsTACI alone prevented production of detectable levels of circulating anti-CII autoantibodies and reduced the severity of arthritis but did not prevent its development. These results indicate that the CII-reactive T cells play a crucial role in the development of CII-induced arthritis and that the anti-CII Abs act to enhance the development of CII-induced arthritis.
Zhang
Huang-Ge
HG
University of Alabama, Birmingham, AL 35294, USA. Huang-Ge.Zhang@cc.uab.edu
Yang
PingAr
P
Xie
Jinfu
J
Liu
Zhongyu
Z
Liu
Di
D
Xiu
Liang
L
Zhou
Tong
T
Wang
Yongming
Y
Hsu
Hui-Chen
HC
Mountz
John D
JD
D000256:Adenoviridae / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000637:transplantation; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis; D019898:Autocrine Communication / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002464:Cell Migration Inhibition; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004359:Drug Therapy, Combination; D053222:Fas Ligand Protein; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D051034:Inhibitor of Apoptosis Proteins; D008213:Lymphocyte Activation / Q000235:genetics; D008212:Lymphocyte Depletion / Q000379:methods; D017737:Macrophages, Peritoneal / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D013753:Tetracycline Resistance / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D053303:Transmembrane Activator and CAML Interactor Protein; D014764:Viral Proteins / Q000235:genetics
D001323:Autoantibodies; D024043:Collagen Type II; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C486361:Tnfrsf13b protein, mouse; D015534:Trans-Activators; D053303:Transmembrane Activator and CAML Interactor Protein; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus