In YivoMigration of Tonsil Lymphocytes in Rheumatoid Synovial Tissue Engrafted in SCID Mice: Involvement of LFA-1

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Abstract
Integrin-adressin binding is a critical step in lymphocty attachment to target tissues. The mucosal recognition systems (αEβ7, α4β7, MADcam-1) have been implicated in the autoimmue 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 αEβ7 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 αEβ7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731 ± 8297 cpm/200 pixel) versus 5982 ± 4713 cpm/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 αEβ7 (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 αEβ7 integrin is involved in tonsil MNC binding to synovial tissue in RA.