Prolongation of allograft and xenograft survival in mice by anti-CD2 monoclonal antibodies.
Anti-CD2 monoclonal antibodies (mAb) were used to influence graft survival in two transplantation models. Xenogeneic rat islets were transplanted intraportally into mice. Anti-CD2 mAb prolonged xenograft survival and was synergistic with UVB irradiation in prolonging survival. Anti-CD2 mAb was also more potent than an anti-CD4 mAb in this model. Allogeneic cardiac grafts were transplanted across an entire H-2 difference and anti-CD2 mAb prolonged allograft survival in a dose-dependent fashion. Kinetic experiments revealed that anti-CD2 mAb was most potent when administered at the time of allografting. A delay in administration of mAb markedly reduced its immunosuppressive effects. Furthermore, additional doses of mAb given after the initial doses provided no increased immunosuppression and anti-CD2 mAbs did not delay rejection of second-set allografts. These findings support the notion that anti-CD2 mAbs interfere with afferent immunity and that CD2 is most important during the initial steps of an immune response. Investigation of the effect of anti-CD2 mAb on cellular immune functions demonstrated, in agreement with previous results, that it caused antigenic down-modulation of CD2 with relative sparing of CD3, CD4, and CD8 cell surface expression. Concomitantly the MLR, CTL, and NK responses were suppressed.
Chavin
K D
KD
Department of Surgery, Medical University of South Carolina, Charleston 29425.
Lau
H T
HT
Bromberg
J S
JS
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D003602:Cytotoxicity, Immunologic; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011971:Receptors, Immunologic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D011971:Receptors, Immunologic