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*
Schepens Eye Research Institute, Harvard Medical School, Boston MA 02114;
Core Research and Evolutional Science and Technology Project (CREST), and Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan;
Cancer Biology Program, Hematology/Oncology Division, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; and
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
In a model of systemic tolerance called Anterior Chamber-Associated
Immune Deviation (ACAID), the differentiation of the T regulatory (Tr)
cells depends on NK T cells and occurs in the spleen. We now show that
the CD1d-reactive NK T cell subpopulation, required for development of
systemic tolerance, expresses the invariant V
14J281 TCR because
J281 knockout (KO) mice were unable to generate Ag-specific Tr cells
and ACAID. The mechanism for NK T cell-dependent differentiation of
Ag-specific Tr cells mediating systemic tolerance was studied by
defining the cytokine profiles in heterogeneous and enriched NK T
spleen cells. In contrast to there being no differences in most
regulatory cytokine mRNAs, both mRNA and protein for IL-10 were
increased in splenic NK T cells of anterior chamber (a.c.)-inoculated
mice. However, IL-10 mRNA was not increased in spleens after i.v.
inoculation. Finally, NK T cells from wild-type (WT) mice, but not from
IL-10 KO mice, reconstituted the ACAID inducing ability in J281 KO
mice. Thus, NK T cell-derived IL-10 is critical for the generation of
the Ag-specific Tr cells and systemic tolerance induced to
eye-inoculated Ags.
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D. E. Faunce and J. Stein-Streilein NKT Cell-Derived RANTES Recruits APCs and CD8+ T Cells to the Spleen During the Generation of Regulatory T Cells in Tolerance J. Immunol., July 1, 2002; 169(1): 31 - 38. [Abstract] [Full Text] [PDF]
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L. T. Mars, V. Laloux, K. Goude, S. Desbois, A. Saoudi, L. Van Kaer, H. Lassmann, A. Herbelin, A. Lehuen, and R. S. Liblau Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice J. Immunol., June 15, 2002; 168(12): 6007 - 6011. [Abstract] [Full Text] [PDF]
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C. P. Gray, P. Arosio, and P. Hersey Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells Blood, May 1, 2002; 99(9): 3326 - 3334. [Abstract] [Full Text] [PDF]
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S. SHARIF, G. A. ARREAZA, P. ZUCKER, and T. L. DELOVITCH Regulatory Natural Killer T Cells Protect against Spontaneous and Recurrent Type 1 Diabetes Ann. N.Y. Acad. Sci., April 1, 2002; 958(1): 77 - 88. [Abstract] [Full Text] [PDF]
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T. Takahashi, S. Chiba, M. Nieda, T. Azuma, S. Ishihara, Y. Shibata, T. Juji, and H. Hirai Cutting Edge: Analysis of Human V{alpha}24+CD8+ NK T Cells Activated by {alpha}-Galactosylceramide-Pulsed Monocyte-Derived Dendritic Cells J. Immunol., April 1, 2002; 168(7): 3140 - 3144. [Abstract] [Full Text] [PDF]
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K.-H. Sonoda, M. Taniguchi, and J. Stein-Streilein Long-Term Survival of Corneal Allografts Is Dependent on Intact CD1d-Reactive NKT Cells J. Immunol., February 15, 2002; 168(4): 2028 - 2034. [Abstract] [Full Text] [PDF]
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M. J. Smyth, N. Y. Crowe, D. G. Pellicci, K. Kyparissoudis, J. M. Kelly, K. Takeda, H. Yagita, and D. I. Godfrey Sequential production of interferon-gamma by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of alpha -galactosylceramide Blood, February 15, 2002; 99(4): 1259 - 1266. [Abstract] [Full Text] [PDF]
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A. Suto, H. Nakajima, K. Ikeda, S. Kubo, T. Nakayama, M. Taniguchi, Y. Saito, and I. Iwamoto CD4+CD25+ T-cell development is regulated by at least 2 distinct mechanisms Blood, January 15, 2002; 99(2): 555 - 560. [Abstract] [Full Text] [PDF]
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L. S. Metelitsa, O. V. Naidenko, A. Kant, H.-W. Wu, M. J. Loza, B. Perussia, M. Kronenberg, and R. C. Seeger Human NKT Cells Mediate Antitumor Cytotoxicity Directly by Recognizing Target Cell CD1d with Bound Ligand or Indirectly by Producing IL-2 to Activate NK Cells J. Immunol., September 15, 2001; 167(6): 3114 - 3122. [Abstract] [Full Text] [PDF]
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D. G. Pellicci, K. J.L. Hammond, A. P. Uldrich, A. G. Baxter, M. J. Smyth, and D. I. Godfrey A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1-CD4+ CD1d-dependent Precursor Stage J. Exp. Med., March 25, 2002; 195(7): 835 - 844. [Abstract] [Full Text] [PDF]
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