The progression of the inflammation in established collagen-induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities.
Alterations in the progression of the inflammatory disease in mice with established collagen-induced arthritis (CIA) by in vivo treatments with either anti-T cell antibodies or an immunosuppressive drug, whose main targets of action are T cells, were studied. It was demonstrated that the in vivo administration of either monoclonal anti-L3T4, anti-Ly-2 or the combination of anti-L3T4 and anti-Ly-2 failed to modify the inflammatory disease after the arthritis had been initiated. Nevertheless, the progression of disease was decreased by treatments with rabbit anti-mouse lymphocyte sera (ALS) in mice with established CIA. While there was a substantial reduction in the proliferative responses to the T cell mitogen concanavalin A (Con A) in these ALS-treated mice, proliferation to a B cell mitogen, lipopolysaccharide, was unaffected. Furthermore, treatments with anti-Thy-1.2 monoclonal antibody (mAb) by itself did not alter the progression of the ongoing inflammatory disease, but combined treatments with both anti-Thy-1.2 and anti-L3T4 mAb prevented the further advancement of the arthritic disease. Although mice receiving either anti-Thy-1.2 alone or both anti-Thy-1.2 and anti-L3T4 exhibited complete absence of Thy-1+ cells within their inguinal lymph nodes, the proliferative responses to Con A by LN cells from mice treated with the combination of anti-Thy-1.2 and anti-L3T4 were drastically reduced compared to the responses of either the anti-Thy-1.2 or anti-L3T4-treated groups. Finally, daily treatments with cyclosporin A, an immunosuppressive drug which preferentially acts on T cells, were also effective in modifying the clinical course of the arthritic disease in mice with established CIA. These results suggest that immunocompetent cells which express the Thy-1 surface marker, most likely Thy-1+ T cells, may play a role in maintaining and perpetuating the inflammatory disease of established CIA.
Hom
J T
JT
Department of Immunology, Lilly Research Laboratories, Indianapolis, IN 46285.
Butler
L D
LD
Riedl
P E
PE
Bendele
A M
AM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001168:Arthritis / Q000517:prevention & control*; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen; D003524:Cyclosporins / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D003094:Collagen