Intrathymic NKT cell development is blocked by the presence of alpha-galactosylceramide.
NKT cell development takes place in the thymus, beginning when these cells branch away from CD4+CD8+ mainstream thymocytes upon expression of the Valpha14Jalpha18 T cell receptor (TCR) and recognition of the CD1d molecule. Although NKT cells express an invariant TCR alpha chain, the diverse TCR beta expression leaves open the possibility that the development of these cells is shaped by glycolipid antigen recognition in the context of CD1d. Here, we show that the presence of an agonist glycolipid ligand, alpha-galactosylceramide, while NKT cells are developing in vitro or in vivo, specifically ablates their development. In contrast, the delayed introduction of this compound in vitro or in vivo, after NKT cells have developed, does not deplete these cells. These data indicate that NKT cells pass through a developmental window where they are susceptible to TCR-mediated negative selection, and suggest that NKT cells with a potentially high level of self reactivity can be removed from the NKT cell repertoire before they exit the thymus.
Pellicci
Daniel G
DG
Department of Pathology and Immunology, Monash University Central and Eastern Clinical School, Commercial Road, Prahran, Victoria 3181, Australia.
Uldrich
Adam P
AP
Kyparissoudis
Konstantinos
K
Crowe
Nadine Y
NY
Brooks
Andrew G
AG
Hammond
Kirsten J L
KJ
Sidobre
Stephané
S
Kronenberg
Mitchell
M
Smyth
Mark J
MJ
Godfrey
Dale I
DI
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000494:pharmacology*
D000519:alpha-Galactosidase