title: Coexistence of Th1- and Th2-type cytokine profiles in anti-CD2 monoclonal antibody-induced tolerance.
abstract: Anti-CD2 monoclonal antibody OX34 has been shown to suppress immunity in rodents in vitro and in vivo. To evaluate the effects of OX34 on vascularized allografts, Lewis (RT1(1)) hearts were transplanted heterotopically into Wistar Furth (RT1(u)) rats. A single 5 mg/kg intraperitoneal dose of OX34 administered at transplantation induced indefinite graft survival (mean survival time >140.3+/-12.3 vs. 12.7+/-0.7 control, P=0.001). The mixed lymphocyte response was partially inhibited at 60 days after transplant, returning to normal at 100 days. Donor-specific tolerance was confirmed by acceptance of second donor (>100 days, n=2) and rejection of third-party (mean survival time: 7.5+/-0.5 days, n=2) hearts. Immunohistochemical staining of allograft tissue from tolerant animals demonstrated abundant CD2+, CD4+, and CD8+ graft-infiltrating cells. To elucidate further the nature of these cells, we compared the expression of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma mRNA in allografted tissue from tolerant, acutely rejecting (AR), isografted, and naive animals using nonisotopic in situ hybridization. A significant increase in IL-2, IL-4, IL-10, and IFN-gamma mRNA was observed in graft-infiltrating cells of both tolerant and AR animals. IL-10 mRNA expression 4 days after transplant was significantly elevated in the OX34-treated compared to AR recipients. These data demonstrate that a single dose of OX34 at engraftment induces tolerance to vascularized allografts. Expression of both T helper 1 and T helper 2 cytokine mRNA profiles (IL-2/IFN-gamma and IL-4/ IL-10, respectively) are up-regulated locally in graft-infiltrating cells of AR and tolerant animal allografts.
authors.affiliation: Department of Surgery, Stanford University, California 94305, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Krieger
authors.forename: D
authors.initials: D
authors.lastname: Most
authors.forename: J S
authors.initials: JS
authors.lastname: Bromberg
authors.forename: B
authors.initials: B
authors.lastname: Holm
authors.forename: P
authors.initials: P
authors.lastname: Huie
authors.forename: R K
authors.initials: RK
authors.lastname: Sibley
authors.forename: D C
authors.initials: DC
authors.lastname: Dafoe
authors.forename: E J
authors.initials: EJ
authors.lastname: Alfrey
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D016130:Immunophenotyping; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D016207:Cytokines