HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, Y. Articles by Yoon, J.-W. Search for Related Content PubMed PubMed Citation Articles by Yang, Y. Articles by Yoon, J.-W. Pubmed/NCBI databases Substance via MeSH

Control of NKT Cell Differentiation by Tissue-Specific Microenvironments ¹

Yang Yang^2,*, Aito Ueno^*, Min Bao, Zhongying Wang^*, Jin Seon Im, Steven Porcelli and Ji-Won Yoon^2,3,

Departments of ^* Biochemistry and Molecular Biology and Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461

CD1d-restricted V14 NKT cells play an important role in both Th1- and Th2-type immune responses. To determine whether NKT cells develop two functionally distinct subsets that provoke different types of responses, we examined the phenotypes and cellular functions of NK1.1⁺ and DX5⁺ T cells. We found that both NK1.1⁺ and DX5⁺ T cells are CD1d-restricted V14 T cells with identical Ag specificities, phenotypes, tissue locations, and functions. Similar to the NK1.1 marker, the DX5 marker (CD49b) is expressed on mature NKT cells in both NK1.1 allele-positive and allele-negative strains. However, when NK1.1⁺ and DX5⁺ NKT cells isolated from different tissues were compared, we found that thymic and splenic NKT cells differed not only in their cytokine profiles, but also in their phenotype and requirements for costimulatory signals. Thymic NKT cells displayed the phenotype of activated T cells and could be fully activated by TCR ligation. In contrast, splenic NKT cells displayed the phenotype of memory T cells and required a costimulatory signal for activation. Furthermore, the function and phenotype of thymic and splenic NKT cells were modulated by APCs from various tissues that expressed different levels of costimulatory molecules. Modulation of NKT cell function and differentiation may be mediated by synergic effects of costimulatory molecules on the surface of APCs. The results of the present study suggest that the costimulatory signals of tissue-specific APCs are key factors for NKT cell differentiation, and these signals cannot be replaced by anti-CD28 or anti-CD40 ligand Abs.

This article has been cited by other articles:

				D. Vallois, M.-C. Gagnerault, P. Avner, U. C. Rogner, C. Boitard, K. Benlagha, A. Herbelin, and F. Lepault Influence of a Non-NK Complex Region of Chromosome 6 on CD4+ Invariant NK T Cell Homeostasis J. Immunol., August 1, 2008; 181(3): 1753 - 1759. [Abstract] [Full Text] [PDF]

				O. Akbari, P. Stock, E. H. Meyer, G. J. Freeman, A. H. Sharpe, D. T. Umetsu, and R. H. DeKruyff ICOS/ICOSL Interaction Is Required for CD4+ Invariant NKT Cell Function and Homeostatic Survival J. Immunol., April 15, 2008; 180(8): 5448 - 5456. [Abstract] [Full Text] [PDF]

				Y. Chung, R. Nurieva, E. Esashi, Y.-H. Wang, D. Zhou, L. Gapin, and C. Dong A Critical Role of Costimulation during Intrathymic Development of Invariant NK T Cells J. Immunol., February 15, 2008; 180(4): 2276 - 2283. [Abstract] [Full Text] [PDF]

				L. Cheng, A. Ueno, S. Cho, J. S. Im, S. Golby, S. Hou, S. A. Porcelli, and Y. Yang Efficient Activation of V{alpha}14 Invariant NKT Cells by Foreign Lipid Antigen Is Associated with Concurrent Dendritic Cell-Specific Self Recognition J. Immunol., March 1, 2007; 178(5): 2755 - 2762. [Abstract] [Full Text] [PDF]

				J. Irie, Y. Wu, K. Kachapati, R. S. Mittler, and W. M. Ridgway Modulating Protective and Pathogenic CD4+ Subsets via CD137 in Type 1 Diabetes Diabetes, January 1, 2007; 56(1): 186 - 196. [Abstract] [Full Text] [PDF]

				K.-i. Seino and M. Taniguchi Functionally distinct NKT cell subsets and subtypes J. Exp. Med., December 19, 2005; 202(12): 1623 - 1626. [Abstract] [Full Text] [PDF]

				N. Y. Crowe, J. M. Coquet, S. P. Berzins, K. Kyparissoudis, R. Keating, D. G. Pellicci, Y. Hayakawa, D. I. Godfrey, and M. J. Smyth Differential antitumor immunity mediated by NKT cell subsets in vivo J. Exp. Med., November 7, 2005; 202(9): 1279 - 1288. [Abstract] [Full Text] [PDF]

				D. G. Pellicci, K. J. L. Hammond, J. Coquet, K. Kyparissoudis, A. G. Brooks, K. Kedzierska, R. Keating, S. Turner, S. Berzins, M. J. Smyth, et al. DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells J. Immunol., October 1, 2005; 175(7): 4416 - 4425. [Abstract] [Full Text] [PDF]

				M. Maeda, C. Carpenito, R. C. Russell, J. Dasanjh, L. L. Veinotte, H. Ohta, T. Yamamura, R. Tan, and F. Takei Murine CD160, Ig-Like Receptor on NK Cells and NKT Cells, Recognizes Classical and Nonclassical MHC Class I and Regulates NK Cell Activation J. Immunol., October 1, 2005; 175(7): 4426 - 4432. [Abstract] [Full Text] [PDF]

				A. P. Uldrich, N. Y. Crowe, K. Kyparissoudis, D. G. Pellicci, Y. Zhan, A. M. Lew, P. Bouillet, A. Strasser, M. J. Smyth, and D. I. Godfrey NKT Cell Stimulation with Glycolipid Antigen In Vivo: Costimulation-Dependent Expansion, Bim-Dependent Contraction, and Hyporesponsiveness to Further Antigenic Challenge J. Immunol., September 1, 2005; 175(5): 3092 - 3101. [Abstract] [Full Text] [PDF]

				M. S. Duthie, M. Kahn, M. White, R. P. Kapur, and S. J. Kahn Both CD1d Antigen Presentation and Interleukin-12 Are Required To Activate Natural Killer T Cells during Trypanosoma cruzi Infection Infect. Immun., March 1, 2005; 73(3): 1890 - 1894. [Abstract] [Full Text] [PDF]