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.
Department of Surgery, Medical University of South Carolina, Charleston 29425.
K D
KD
Chavin
H T
HT
Lau
J S
JS
Bromberg
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