title: Regulation by differential development of Th1 and Th2 cells in peripheral tolerance to cardiac allograft induced by blocking ICAM-1/LFA-1 adhesion.
abstract: BACKGROUND
  Specific immune tolerance to cardiac allografts is induced by anti-ICAM-1 and anti-LFA-1 MAbs. Although the expression of the Th1 cytokines IL-2 and IFN-gamma is shown to increase in association with acute rejection, the roles of cytokines in the induction of peripheral tolerance by anti-ICAM-1 and anti-LFA-1 MAbs are not yet known.
  
  
  RESULTS
  BALB/c hearts were transplanted into C3H/He mice. The MAbs to ICAM-1 and LFA-1 were injected for 3 days after transplantation in some recipients, and others were treated with FK506. IL-2 concentration in the supernatant of splenocytes from MAb-treated mice that were mix-cultured with donor splenocytes was lower than in normal controls. The expression of Th1 cytokines, detected by Northern blot assay, was enhanced in grafts or spleens of nontreated mice, whereas Th2 cytokines were expressed in the spleens of MAb-treated mice. No cytokine expression was enhanced in mice treated with FK506. Also, the induction of tolerance was prevented by the administration of rIL-2 in vivo in 5 of 7 mice, which were rendered tolerant.
  
  
  CONCLUSIONS
  These data provide evidence that impairment of IL-2 production is critically involved in this tolerance induction and suggest that predominance of Th2 over Th1 cells is essential for tolerance induction by antiadhesion therapy.
authors.affiliation: First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. isobemi@gipac.shinshu-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Isobe
authors.forename: J
authors.initials: J
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: S
authors.initials: S
authors.lastname: Horie
authors.forename: Y
authors.initials: Y
authors.lastname: Okubo
authors.forename: K
authors.initials: K
authors.lastname: Maemura
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007165:Immunosuppression Therapy / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma