Amelioration of acute graft-versus-host disease by NKG2A engagement on donor T cells.
Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic bone marrow transplantation, which is caused by donor T cells specific for host alloantigens. In a murine model, we found that donor T cells expressed a natural killer cell inhibitory receptor, CD94/NKG2A, during the course of aGVHD. Administration of an anti-NKG2A mAb markedly inhibited the expansion of donor T cells and ameliorated the aGVHD pathologies. These results suggested that the CD94/NKG2A inhibitory receptor expressed on host-reactive donor T cells can be a novel target for the amelioration of aGVHD.
Kawamura
Hiroki
H
Department of Immunology, Niigata University School of Medicine, Niigata, Japan. h-kawa@med.niigata-u.ac.jp
Yagita
Hideo
H
Nisizawa
Tetsuro
T
Izumi
Nakako
N
Miyaji
Chikako
C
Vance
Russell E
RE
Raulet
David H
DH
Okumura
Ko
K
Abo
Toru
T
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C527057:Klrc1 protein, mouse; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell