Prolongation of allogeneic skin graft survival by injection of anti-Ly49A monoclonal antibody YE1/48.
Ly49A receptors expressed on NK, NKT, and T cells play inhibitory roles in regulating the immune responses in vivo and in vitro. Whether or not injection of anti-Ly49A monoclonal antibody (mAb) YE1/48 can block allograft rejection has not been evaluated. Balb/c mouse recipients received intraperitoneal injections of YE1/48 mAb (0.5 mg) or control mAb or phosphate-buffered saline on days -1 and 10. On day 0, fully MHC-mismatched allogeneic C57BL/6 (B6) skin grafts were implanted. The skin graft survival and anti-donor humoral responses were observed. Whereas allogeneic B6 skin grafts survived 14 days in isotopy control antibody-treated or nontreated Balb/c mice, injection of YE1/48 mAb significantly prolonged B6 skin graft survival to 19 days (P < 0.0005). Injection of YE1/48 mAb into presensitized Balb/c recipients did not significantly delay B6 skin graft rejection. On the other hand, after depleting recipient NK, NKT, and some cytotoxic T cells by injection of anti-asialo GM1, YE1/48 failed to prolong B6 skin graft survival in Balb/c recipients. The present studies indicate that injection of YE1/48 mAb significantly delays allogeneic skin graft rejection in nonsensitized recipients but not in sensitized recipients. The presence of NK, NKT cells, and some cytotoxic T cells may be essential for YE1/48-mediated immunosuppression in vivo.
Yang
Tian-Yu
TY
Department of Surgery, University of Nebraska Medical Center, The Lied Transplant Center, 987690 University of Nebraska Medical Center, Omaha, NE 68198-7690, USA.
Sun
Yimin
Y
Langnas
Alan N
AN
Zhao
Yong
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000918:Antibody Specificity; D000950:Antigens, Ly / Q000276:immunology*; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007518:Isoantibodies / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007518:Isoantibodies; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like