CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity.
CD1d-restricted T-cells are activated by glycolipids presented by the major histocompatibility complex class-Ib molecule CD1d, found on the surface of antigen-presenting cells (APC). This interaction between APC, most notably dendritic cells (DC), and CD1d-restricted T-cells is an important regulatory step in the initiation of adaptive immune responses. It is well known that DC play a crucial role in the induction of contact hypersensitivity (CHS), a frequently studied form of in vivo T-cell-mediated immunity. In this study, we show that CD1d-restricted T-cells are also necessary for CHS, because both wild-type mice treated systemically or topically with CD1d glycolipid antagonists and CD1d-restricted T-cell-null mice have markedly diminished CHS responses. Thus, pharmacologic antagonists of CD1d can be used as effective inhibitors of CHS, a prototype for a variety of delayed-type tissue hypersensitivity responses.
Nieuwenhuis
Edward E S
EE
Gastrointestinal Division, Brigham and Women's Hospital, Boston, MA, USA.
Gillessen
Silke
S
Scheper
Rik J
RJ
Exley
Mark A
MA
Taniguchi
Masaru
M
Balk
Steven P
SP
Strominger
Jack L
JL
Dranoff
Glenn
G
Blumberg
Richard S
RS
Wilson
S Brian
SB
D000287:Administration, Topical; D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism / Q000502:physiology*; D055610:Antigens, CD1d; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology; D003872:Dermatitis / Q000473:pathology; D003877:Dermatitis, Contact / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006017:Glycolipids / Q000737:chemistry; D006967:Hypersensitivity; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010081:Oxazolone / Q000737:chemistry / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism
D018949:Antigens, CD1; D055610:Antigens, CD1d; C102564:DPPE-PEG2000; D006017:Glycolipids; D010714:Phosphatidylethanolamines; D011948:Receptors, Antigen, T-Cell; D010081:Oxazolone; D011092:Polyethylene Glycols