TY - JOUR
T1 - Direct regulatory role of NKT cells in allogeneic graft survival is dependent on the quantitative strength of antigenicity
AU - Oh, Keunhee
AU - Kim, Sanghee
AU - Park, Se Ho
AU - Gu, Hua
AU - Roopenian, Derry
AU - Doo, Hyun Chung
AU - Yon, Su Kim
AU - Lee, Dong Sup
PY - 2005/2/15
Y1 - 2005/2/15
N2 - The role of NKT cells during immune responses is diverse, ranging from antiviral and antitumor activity to the regulation of autoimmune diseases; however, the regulatory function of CD1d-dependent NKT cells in rejection responses against allogeneic graft is uncertain. In this study, we demonstrated the direct regulatory effects of CD1d-dependent NKT cells using an allogeneic skin transplantation model. H-Y-mismatched skin graft survival was shortened in CD1d-/- recipients compared with wild-type recipients. Adoptive transfer of syngeneic NKT cells via splenocytes or hepatic mononuclear cells into CD1d-/- recipients restored graft survival times to those of wild-type recipients. α-Galactosylceramide, a specific activator of NKT cells, further prolonged graft survival. Although CD1d-dependent NKT cells did not extend skin graft survival in either major or complete minor histocompatibility-mismatched models, these cells affected graft survival in minor Ag mismatch models according to the magnitude of the antigenic difference. The afferent arm of NKT cell activation during transplantation required CD1d molecules expressed on host APCs and the migration of CD1d-dependent NKT cells into grafts. Moreover, the regulatory effects of CD1d-dependent NKT cells against alloantigen were primarily IL-10 dependent. Taken together, we concluded that CD1d-dependent NKT cells may directly affect the ontcome of allogeneic skin graft through an IL-10-dependent regulatory mechanism.
AB - The role of NKT cells during immune responses is diverse, ranging from antiviral and antitumor activity to the regulation of autoimmune diseases; however, the regulatory function of CD1d-dependent NKT cells in rejection responses against allogeneic graft is uncertain. In this study, we demonstrated the direct regulatory effects of CD1d-dependent NKT cells using an allogeneic skin transplantation model. H-Y-mismatched skin graft survival was shortened in CD1d-/- recipients compared with wild-type recipients. Adoptive transfer of syngeneic NKT cells via splenocytes or hepatic mononuclear cells into CD1d-/- recipients restored graft survival times to those of wild-type recipients. α-Galactosylceramide, a specific activator of NKT cells, further prolonged graft survival. Although CD1d-dependent NKT cells did not extend skin graft survival in either major or complete minor histocompatibility-mismatched models, these cells affected graft survival in minor Ag mismatch models according to the magnitude of the antigenic difference. The afferent arm of NKT cell activation during transplantation required CD1d molecules expressed on host APCs and the migration of CD1d-dependent NKT cells into grafts. Moreover, the regulatory effects of CD1d-dependent NKT cells against alloantigen were primarily IL-10 dependent. Taken together, we concluded that CD1d-dependent NKT cells may directly affect the ontcome of allogeneic skin graft through an IL-10-dependent regulatory mechanism.
UR - http://www.scopus.com/inward/record.url?scp=13544262688&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.174.4.2030
DO - 10.4049/jimmunol.174.4.2030
M3 - Article
C2 - 15699132
AN - SCOPUS:13544262688
SN - 0022-1767
VL - 174
SP - 2030
EP - 2036
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -