In vivo migration of tonsil lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: involvement of LFA-1.
Integrin-adressin binding is a critical step in lymphocte attachment to target tissues. The mucosal recognition systems (alpha E beta 7, alpha 4 beta 7, MADcam-1) have been implicated in the autoimmune process in rheumatoid arthritis. We developed a model for in vivo study of radio-labelled lymphocyte circulation and their attachment to human rheumatoid synovium. We studied the homing of tonsil lymphocytes, considered as mucosal lymphocytes, and the involvement of alpha E beta 7 integrin and LFA1 in the homing of tonsil lymphocytes. We engrafted human rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks later, we injected intraperitoneally 20 IO6 human peripheral blood or tonsil mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total body scintigram was obtained 20 h postinjection. The same protocol was performed after treatment of the MNC and mAb against LFA-1 (CD11a) or alpha E beta 7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731 +/- 8297cpm/200 pixel) versus 5982 +/- 4713cpm/200 pixel, p < 0.05). A monoclonal antibody against LFA 1 decreased the activity in the graft (4152 +/- 1287 cpm/200 pixel), p < 0.05. No significant difference in tonsil MNC attachment to rheumatoid synovial tissue was observed with a mAb against alpha E beta 7 (8057 +/- 5009 cpm/200 pixel). Our results showed an increase in radiolabelled mucosal MNC migration in synovial tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest that LFA-1 but not the alpha E beta 7 integrin is involved in tonsil MNC binding to synovial tissue in RA.
Jorgensen
C
C
Service d'Immuno-Rhumatologie Hôpital Lapeyronie, Montpellier, France.
Couret
I
I
Canovas
F
F
Bologna
C
C
Brochier
J
J
Reme
T
T
Sany
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D006801:Humans; D039001:Integrin alpha Chains; D016023:Integrins / Q000032:analysis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology*; D013583:Synovial Membrane / Q000637:transplantation*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; C091367:alpha E integrins; C070709:integrin alphaEbeta7