Host-residual invariant NK T cells attenuate graft-versus-host immunity.
Invariant NK T (iNKT) cells have an invariant TCR-alpha chain and are activated in a CD1d-restricted manner. They are thought to regulate immune responses and play important roles in autoimmunity, allergy, infection, and tumor immunity. They also appear to influence immunity after hemopoietic stem cell transplantation. In this study, we examined the role of iNKT cells in graft-vs-host disease (GVHD) and graft rejection in a mouse model of MHC-mismatched bone marrow transplantation, using materials including alpha-galactosylceramide, NKT cells expanded in vitro, and Jalpha18 knockout mice that lack iNKT cells. We found that host-residual iNKT cells constitute effector cells which play a crucial role in reducing the severity of GVHD, and that this reduction is associated with a delayed increase in serum Th2 cytokine levels. Interestingly, we also found that host-residual iNKT cause a delay in engraftment and, under certain conditions, graft rejection. These results indicate that host-residual iNKT cells attenuate graft-vs-host immunity rather than host-vs-graft immunity.
Departments of Hematology/Oncology, Cell Therapy/Transplantation Medicine, University of Tokyo Graduate School of Medicine and Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Kyoko
K
Haraguchi
Tsuyoshi
T
Takahashi
Akihiko
A
Matsumoto
Takashi
T
Asai
Yoshinobu
Y
Kanda
Mineo
M
Kurokawa
Seishi
S
Ogawa
Hideaki
H
Oda
Masaru
M
Taniguchi
Hisamaru
H
Hirai
Shigeru
S
Chiba
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000494:pharmacology; D006082:Graft Enhancement, Immunologic / Q000379:methods; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D006358:Hot Temperature; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*
D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide