Control of NKT Cell Differentiation by Tissue-Specific Microenvironments

Yang Yang, Aito Ueno, Min Bao, Zhongying Wang, Jin Seon Im, Steven A. Porcelli, Ji Won Yoon

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

CD1d-restricted Vα14 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 Vα14 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.

Original languageEnglish (US)
Pages (from-to)5913-5920
Number of pages8
JournalJournal of Immunology
Volume171
Issue number11
StatePublished - Dec 1 2003

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Natural Killer T-Cells
Cell Differentiation
Phenotype
T-Lymphocytes
Alleles
CD40 Ligand
Organ Specificity
Ligation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Yang, Y., Ueno, A., Bao, M., Wang, Z., Im, J. S., Porcelli, S. A., & Yoon, J. W. (2003). Control of NKT Cell Differentiation by Tissue-Specific Microenvironments. Journal of Immunology, 171(11), 5913-5920.

Control of NKT Cell Differentiation by Tissue-Specific Microenvironments. / Yang, Yang; Ueno, Aito; Bao, Min; Wang, Zhongying; Im, Jin Seon; Porcelli, Steven A.; Yoon, Ji Won.

In: Journal of Immunology, Vol. 171, No. 11, 01.12.2003, p. 5913-5920.

Research output: Contribution to journalArticle

Yang, Y, Ueno, A, Bao, M, Wang, Z, Im, JS, Porcelli, SA & Yoon, JW 2003, 'Control of NKT Cell Differentiation by Tissue-Specific Microenvironments', Journal of Immunology, vol. 171, no. 11, pp. 5913-5920.
Yang Y, Ueno A, Bao M, Wang Z, Im JS, Porcelli SA et al. Control of NKT Cell Differentiation by Tissue-Specific Microenvironments. Journal of Immunology. 2003 Dec 1;171(11):5913-5920.
Yang, Yang ; Ueno, Aito ; Bao, Min ; Wang, Zhongying ; Im, Jin Seon ; Porcelli, Steven A. ; Yoon, Ji Won. / Control of NKT Cell Differentiation by Tissue-Specific Microenvironments. In: Journal of Immunology. 2003 ; Vol. 171, No. 11. pp. 5913-5920.
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