title: Differential Th1 and Th2 cell regulation of murine cardiac allograft acceptance by blocking cell adhesion of ICAM-1/LFA-1 and VCAM-1/VLA-4.
abstract: Administration of anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody (mAb) plus anti-lymphocyte function associated antigen (LFA)-1 mAb induces tolerance in murine cardiac transplantation, while anti-vascular cell adhesion molecule (VCAM)-1 mAb plus anti-very late antigen (VLA)-4 mAb administration prolongs graft survival, but leads to tolerance only in some cases. BALB/c mice hearts were transplanted into C3H/He recipients. Each combination of anti-VCAM-1 plus anti-VLA-4 mAbs (100 microg each/day, i.p.) or anti-ICAM-1 plus anti-LFA-1 mAbs (50 microg each/day, i.p.) was administered for 5 days. For control study, third group mice received daily with FK506 administration (1 mg/kg/day). The cardiac allografts and recipients' spleens were harvested on day 7; the expression of cytokines were detected using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR. Th2 cytokines (IL-4 and IL-10) were markedly enhanced and Th1 cytokines (IFN-gamma and IL-2) were suppressed in recipients treated with anti-ICAM-1 mAb plus anti-LFA-1 mAb, while poor Th2 cytokine expression allowed persistent Th1 cytokine expression in recipient mice with anti-VCAM-1 mAb plus anti-VLA-4 mAb treatment. Both Th1 and Th2 cytokine expression was suppressed in FK506-treated mice. It is concluded that immunological tolerance and prolonged graft survival induced by blocking cell adhesion is regulated by different cytokine expression.
authors.affiliation: Department of Internal Medicine I, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Isobe
authors.forename: A
authors.initials: A
authors.lastname: Izawa
authors.forename: W
authors.initials: W
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Okubo
authors.forename: J
authors.initials: J
authors.lastname: Amano
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1