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李京 Toward An Understanding of NKT cell biology final edition by LiJing

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李京 Toward An Understanding of NKT cell biology final edition by LiJing Powered By Docstoc
					Toward An Understanding of NKT cell
biology:
    Progress and Paradoxes




                      Presented by Li Jing
Catalog for the following 10 minutes
    One Definition
       Characteristics & Distribution
    Two Models of Development
    Three Subsets
    Four Functions
          Control of infection
          Bridging innate and acquired immunity
          Targets for autoimmune disease
          Role in Tumor immunity
    Progress and Paradoxes…
    Concluding Remarks
What is NKT Cells?




              Immunology Today November 2000 Vol21 No.11 573
      Characteristics

   Express both T cell receptors and NK1.1
    receptors — hence its name.
 Respond    to glycolipid antigens presented by
    CD1d
   CD1 restricted rather than MHC restricted
   CD4+ or Double negative, in mice
   Secrete large amounts of either IFN-γ, IL-4,
    TNF
   Lack immunological memory
   Recent Definition

Natural Killer T cells are cells that nearly
always have an
invariant Vα 14-Jα 18 rearrangement
                   and
     reactivity to the α-GalCer.

                  ——Annu. Rev. Immunol. 2005. 26:877–900
         Distribution

   NKT cells can be detected wherever conventional T
    cells are found, in mice
   The ratio of NKT to T cells varies widely in a tissue-
    specific manner
   NKT cells are most frequent in liver (30–50%), bone
    marrow (20–30%) and thymus (10–20%)
   Human NKT cells are most limited in peripheral blood
   The distribution of NKT cells in other human tissues
    remains to be determined.
Development: The Unconventional Life Style




                       Current Opinion in Immunology 2002, 14:250–254
    Subsets
     Classification of NKT and NKT-like cells

              TypeⅠcells                    TypeⅡcells              NKT-like cells
             (Classical NKT cells)      (Non-classical NKT cells)

  CD1d            Yes                          Yes                      No
dependent
 α-GalCer         Yes                           No                      No
 reactive
TCR alpha    Vα14-Jα18
                   (mice)
                                          Diverse                   Diverse
  chain      Vα24-Jα18
                 (human)

   IL-4           Yes                          Yes                      No
production
   IFN-γ          Yes                          Yes                     Yes
production
                                     Nature Reviews immunology volume 4 march 2004. 231
      Functions

 Control   of infection

 Bridging   innate and acquired immunity

 Therapeutic    potential for autoimmune
 diseases

 Tumor   rejection
1.Control of infection




                         Current Biology Vol 15 No 11,2005
2.Bridging innate and acquired immunity




           VOLUME 4 NUMBER 12 DECEMBER 2003 NATURE IMMUNOLOGY
3.Targets for immunotherapy of autoimmune diseases:
modulate TH1-dominant autoimmunity




                      NATURE REVIEWS IMMUNOLOGY VOLUME 5 JANUARY 2005
4.Antitumor immunity: a double-edged sword




                 Immunology and Cell Biology (2004)82, 323–331
Past and Progress…




               Nature Reviews immunology volume 4 march 2004. 231
   Paradoxes and Future…

 What  is the functional differences between
 different types of NKT cells?
 What is the developmental origin and
 developmental process of NTK cells?
 Why   are NKT cells lack of CD8 expression?
 Whether α-Galcer therapy for autoimmune
 diseases can be used in clinic safely?
Concluding remarks

        It is necessary to gain a better
 understanding of the immunological
 properties of human NKT cells, in
 particular of how they differ from mouse
 NKT cells and how they modulate the
 human immune system in response to
 glycolipid activation.
          Presented by Li Jing
          Msn: uniquejli@hotmail.com
          http://www.uniquelink.nease.net
          QQ:56325505



Thank you for your attention!
Supplemental materials




   A marine-sponge derived glycosphingolipid
   The lipid portion of α-GalCer interacts with the hydrophobic
    antigen-binding groove of CD1d, and the carbohydrate portion
    is accessible for interaction with the invariant natural killer T
    (iNKT)-cell T-cell receptor.
Endogenous NKT cell antigens-iGb3




   A breakthrough was made recently by the finding that an
    endogenous, lysosomal glycosphingolipid,
    soglobotrihexosylceramide (iGb3) was required for the
    intrathymic development of NKT cells and was capable of
    activating NKT cells, albeit less potently than α-GalCer
Other Ligands




      Sphingomonas (鞘脂单胞菌属) glycolipids
       can activate NKT cell without the help of
       iGb3
Gene rearrangement to yield a functional gene
encoding the αβ T- cell receptor
Similarities and differences among various NKT cells,
conventional T cells and NK cells in mice




Type I, interferon-gamma; type II, interleukin-4




                                                   TRENDS in Immunology Vol.24 No.7 July 2003
Current Opinion in Immunology 2003, 15:683–689
NKT cells’ development
      in thymus-
     According to
 Mainstream Model




        NATURE REVIEWS |
        IMMUNOLOGY
        VOLUME 2 | AUGUST
        2002 | 557
Two possible ways to modulate autoimmunity




                                   TRENDS in Immunology Vol.25 No.9 September 2004
NATURE REVIEWS IMMUNOLOGY VOLUME 5 JANUARY 2005
              References
Lennart T. Mars et.al, Therapeutic manipulation of iNKT cells in autoimmunity: modes of
   action and potential risks, TRENDS in Immunology Vol.25 No.9 September 2004
Dale I. Godfrey,NKT cells: what’s in a name?, nature reviews immunology volume 4 march
   2004 231
Luc Van Kaer, α-galactosylceramide therapy for autoimmune diseases: prospects and
   obstacles, nature reviews immunology volume 5, january 2005,31
Mitchell Kronenberg,TOWARD AN UNDERSTANDING OF NKT CELL BIOLOGY:
   Progress and Paradoxes, Annu. Rev. Immunol. 2005. 26:877–900
Masaru Taniguchi, The NKT cell system: bridging innate and acquired immunity, volume 4
   number 12 december 2003 nature immunology
Luc Van Kaer, Innate Immunity: NKT Cells in the Spotlight, Current Biology Vol 15 No
   11,2005
Dale I. Godfrey, NKT cells: facts, functions and fallacies, Immunology Today November
   2000 Vol21 No.11 573
             References

Mitchell Kronenberg and Laurent Gapin, THE UNCONVENTIONAL LIFESTYLE OF NKT
   CELLS, nature reviews immunology volume 2 august 2002 557
H Robson MacDonald, Development and selection of NKT cells, Current Opinion in Immunology
    2002, 14:250–254
LUC VAN KAER, Natural killer T cells as targets for immunotherapy of autoimmune diseases,
    Immunology and Cell Biology(2004)82, 315–322
JEREMY SWANN, Regulation of antitumour immunity by CD1d-restricted NKT cells, Immunology
    and Cell Biology(2004)82, 323–331
Masashi Emoto and Stefan H.E. Kaufmann, Liver NKT cells: an account of heterogeneity, TRENDS
    in Immunology Vol.24 No.7 July 2003
Kirsten JL, Natural killer T cells: natural or unnatural regulators of autoimmunity? Current Opinion in
    Immunology 2003, 15:683–689
MARK J. SMYTH, NKT cells and tumor immunity—a double-edged sword, nature immunology,
    december 2000, volume 1 no 6
           Presented by Li Jing
           Msn: uniquejli@hotmail.com
           http://www.uniquelink.nease.net
           QQ:56325505



Thank you for your attention!

				
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