Intrathymic NKT cell development is blocked by the presence of α-galactosylceramide

被引:54
作者
Pellicci, DG
Uldrich, AP
Kyparissoudis, K
Crowe, NY
Brooks, AG
Hammond, KJL
Sidobre, S
Kronenberg, M
Smyth, MJ
Godfrey, DI
机构
[1] Monash Univ, Cent & Eastern Clin Sch, Dept Pathol & Immunol, Prahran, Vic 3181, Australia
[2] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia
[3] La Jolla Inst Allergy & Immunol, Div Dev Immunol, San Diego, CA USA
[4] Peter MacCallum Canc Inst, Sir Donald & Lady Trescowthick Labs, Canc Immunol Program, Melbourne, Vic, Australia
关键词
NKT cell; T lymphocyte; thymus; tolerance;
D O I
10.1002/eji.200323894
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 a 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, cc-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.
引用
收藏
页码:1816 / 1823
页数:8
相关论文
共 36 条
  • [1] Mouse CD1-specific NK1 T cells: Development, specificity, and function
    Bendelac, A
    Rivera, MN
    Park, SH
    Roark, JH
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 : 535 - 562
  • [2] In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers
    Benlagha, K
    Weiss, A
    Beavis, A
    Teyton, L
    Bendelac, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (11) : 1895 - 1903
  • [3] A thymic precursor to the NK T cell lineage
    Benlagha, K
    Kyin, T
    Beavis, A
    Teyton, L
    Bendelac, A
    [J]. SCIENCE, 2002, 296 (5567) : 553 - 555
  • [4] Chen HJ, 1997, J IMMUNOL, V158, P5112
  • [5] Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments
    Chiu, YH
    Jayawardena, J
    Weiss, A
    Lee, D
    Park, SH
    Dautry-Varsat, A
    Bendelac, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (01) : 103 - 110
  • [6] NK1.1+ T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4+CD8+ cells
    Coles, MC
    Raulet, DH
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (05) : 2412 - 2418
  • [7] A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas
    Crowe, NY
    Smyth, MJ
    Godfrey, DI
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (01) : 119 - 127
  • [8] Eberl G, 1999, J IMMUNOL, V162, P6410
  • [9] NKT cells derive from double-positive thymocytes that are positively selected by CDId
    Gapin, L
    Matsuda, JL
    Surh, CD
    Kronenberg, M
    [J]. NATURE IMMUNOLOGY, 2001, 2 (10) : 971 - 978
  • [10] GODFREY DI, 1994, J IMMUNOL, V152, P2729