Reduction of CD4 positive T cells and improvement of pathological changes of collagen-induced arthritis by FTY720.
FTY720 belongs to a new class of immunosuppressants. Little is known about its influence on T cell subtypes and pathological changes in arthritis. Here we illustrated the effect of FTY720 on peripheral T cell subsets and joint damage of collagen-induced arthritis rats. Rats were administered FTY720 or prednisone daily from day 0 to day 28. Body weight, hind paw swelling and arthritis index were measured. Bone destruction was determined by micro-computed tomography and histopathology, and T cell subsets were analyzed by flow cytometry and immunohistochemistry. The results showed that FTY720 inhibited the development of arthritis. Radiological analysis revealed that FTY720 treated collagen-induced arthritic rats had much less joint damage in comparison to untreated collagen-induced arthritic rats. Histological study showed that collagen-induced arthritic rats suffered from inflammatory cell infiltration and synovial hyperplasia in their joints, and FTY720 treatment clearly reduced these pathological changes. Immunohistochemical analysis showed that FTY720 treatment significantly decreased the number of CD4(+) T cells in the synovium of collagen-induced arthritic rats. Collagen-induced arthritic rats appeared to have more CD4(+), but not CD8(+) T cells in their peripheral blood than normal control rats. Following FTY720 treatment, peripheral blood CD3(+) and CD4(+) T cells in collagen-induced arthritic rats were significantly decreased. In conclusion, FTY720 is an effective compound in the treatment of collagen-induced arthritic rats and in reducing CD4(+) T cells in collagen-induced arthritic rats.
Wang
Fang
F
The Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. fangwang7608@263.net
Tan
Wenfeng
W
Guo
Dunming
D
He
Shaoheng
S
D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D015704:CD4 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002645:Chickens; D024043:Collagen Type II / Q000633:toxicity*; D005260:Female; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D005552:Forelimb / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D011241:Prednisone / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
D015704:CD4 Antigens; D016827:CD8 Antigens; D024043:Collagen Type II; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D011241:Prednisone