CD1d-expressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells.
Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid alpha-galactosylceramide (alpha-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vbeta usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen.
Chun
Taehoon
T
Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 East 57th St., R412, Chicago, IL 60637-5420, USA.
Page
Michael J
MJ
Gapin
Laurent
L
Matsuda
Jennifer L
JL
Xu
Honglin
H
Nguyen
Hanh
H
Kang
Hyung-Sik
HS
Stanic
Aleksandar K
AK
Joyce
Sebastian
S
Koltun
Walter A
WA
Chorney
Michael J
MJ
Kronenberg
Mitchell
M
Wang
Chyung-Ru
CR
D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology*; D055610:Antigens, CD1d; D001854:Bone Marrow Cells / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005699:Galactosylceramides / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta