Recruitment and proliferation of CD4+ T cells in synovium following adoptive transfer of adjuvant-induced arthritis.
Adjuvant-induced arthritis can be transferred to naive Dark Agouti (DA) strain (DA.CD45.1) rats by thoracic duct (TD) lymphocytes. Disease can be re-induced in convalescent rats by further transfer of arthritogenic cells, suggesting that resolution of the adoptive disease is not due to active regulation. To examine whether resolution is due to exhaustion of effector cells, we transferred the disease to DA.CD45.1 recipients, using CD4+ T cells from DA.CD45.2 donors. At the height of the adoptively transferred disease, donor cells comprised only 5-10% of recirculating CD4+ T cells but they accounted for approximately 40% of the CD4+ T cells in synovium-rich tissues of the hind paws. Approximately 65% of the donor cells in the synovium expressed a marker of proliferation (Ki-67 antigen). Division of CD4+ T cells continued in shielded paws after suppression of the recirculating pool of lymphocytes by selective irradiation. Intravenously injected CD4+ TD T lymphoblasts from arthritic donors were recruited to normal paws and, in greater numbers, to paws of animals with existing arthritis. Survival of the [125I]iodo-deoxyuridine-labeled lymphoblasts was greater in animals with existing arthritis. We conclude that effector CD4+ T cells in target tissues can proliferate in response to autoantigens and exhibit enhanced survival. However, without a continuous supply, adoptively transferred effector cells do not produce autonomous local disease, due to limits to their lifespan and ability to replicate indefinitely.
Spargo
Llewellyn D J
LD
Arthritis Research Laboratory, Hanson Research Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
Cleland
Leslie G
LG
Cockshell
Michaelia P
MP
Mayrhofer
Graham
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology* / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D017710:Lymphocyte Transfusion; D051381:Rats; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013897:Thoracic Duct / Q000276:immunology / Q000473:pathology; D014965:X-Rays
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse