title: Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/- mice.
abstract: Successful transplantation of allogeneic organs is an important objective in modern medicine. However, sophisticated immune defense mechanisms, primarily evolved to combat infections, often work against medical transplantation. To investigate the roles of natural and adaptive immune responses in transplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in mice. Neither of these interventions alone led to acceptance of allogeneic vascularized cardiac grafts. In contrast, inhibition of NK-receptor-bearing cells combined with CD28-costimulation blockade established long-term graft acceptance. These results indicate a concerted interplay between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor-bearing cells could be a new strategy for successful survival of solid-organ transplants.
authors.affiliation: Department of Surgery, Immunology and Hygiene, Technische Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Maier
authors.forename: C
authors.initials: C
authors.lastname: Tertilt
authors.forename: N
authors.initials: N
authors.lastname: Chambron
authors.forename: K
authors.initials: K
authors.lastname: Gerauer
authors.forename: N
authors.initials: N
authors.lastname: Hüser
authors.forename: C D
authors.initials: CD
authors.lastname: Heidecke
authors.forename: K
authors.initials: K
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D012333:RNA, Messenger