Expression of NKG2D and its ligand in mouse heart allografts may have a role in acute rejection.
BACKGROUND
Ligands for the natural killer cell-activating receptor NKG2D, such as retinoic acid early inducible (Rae-1), minor histocompatibility antigen H60 (mouse), and major histocompatibility complex class I chain-related (human) may be expressed by tissues in response to stress. Because NKG2D-ligand engagement may induce natural killer cell activation and provide T-cell costimulation, we examined whether this interaction between innate and adaptive immunity occurred during heart transplant rejection.


METHODS
Hearts from BALB/c mice were heterotopically transplanted into C57BL/6 mice without immunosupression. Grafts were harvested at 1, 3, and 5 days after transplantation. Rae-1, H60, and NKG2D mRNA were analyzed by RT-PCR, and the proteins were detected by immunohistochemistry.


RESULTS
Compared with no expression in naïve BALB/c mice hearts, Rae-1 mRNA levels in heart allografts were detected from days three to five postoperative, H60 on day five, and NKG2D on day three but prominently on day five postoperative. Immunohistochemical assay showed that compared with rare expression in syngeneic cardiac grafts, there were significant protein expressions of Rae-1 and NKG2D in heart allografts from days three to five postoperative and of H60 on day 5 postoperative.


CONCLUSIONS
This study reported significant mRNA and protein expression of Rae-1, H60, and NKG2D during acute cardiac allograft rejection. The simultaneous and significant expression of NKG2D and its ligands indicated that interactions with innate immunity may promote acute rejection. The results also suggested that Rae-1 and H60 may be new targets to amelioate this immune response.
Feng
L
L
Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu 610041, China.
Ke
N
N
Ye
Z
Z
Guo
Y
Y
Li
S
S
Li
Q
Q
Li
Y
Y
D000208:Acute Disease; D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015395:Histocompatibility Antigens Class I; D008024:Ligands; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012313:RNA