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 Lai, Y.-G. Articles by Liao, N.-S. Search for Related Content PubMed PubMed Citation Articles by Lai, Y.-G. Articles by Liao, N.-S.

IL-15 Promotes Survival But Not Effector Function Differentiation of CD8⁺ TCRß⁺ Intestinal Intraepithelial Lymphocytes¹

Yein-Gei Lai^*, Vasily Gelfanov^2,*, Valentina Gelfanova^2,*, Liudmila Kulik^*, Ching-Liang Chu^*,, Sheau-Wen Jeng^* and Nan-Shih Liao^3,*

^* Institute of Molecular Biology, Academia Sinica, and Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

CD8 single-positive cells, including CD8⁺ and CD8ß⁺ subsets, constitute the majority of TCRß⁺ intestinal intraepithelial lymphocytes (ß iIEL) in mice. CD8⁺ ß iIEL show significantly weaker responses to TCR stimulation in the presence of exogenous IL-2 than do CD8⁺ T cells of the central immune system. IL-15 is a T cell growth factor likely expressed in the intestine mucosa. To understand the role of IL-15 in CD8⁺ ß iIEL biology, we compared the effects of exogenous IL-15 and IL-2 on the survival and primary responses of the two CD8⁺ ß iIEL subsets in vitro. In contrast to the death of 60% of both CD8⁺ and CD8ß⁺ iIEL cultured in IL-2 with or without TCR stimulation, IL-15 promoted survival of the CD8⁺ subset in the presence of TCR stimulation and promoted survival of both subsets in the absence of TCR stimulation. The higher proliferation level of TCR stimulated CD8⁺ ß iIEL cultured in IL-15 compared with those cultured in IL-2 is likely due to IL-15’s prosurvival effects. In addition, unlike exogenous IL-2, exogenous IL-15 did not support the effector functions of either iIEL subsets, including IFN- production, IL-4-induced Th2 cytokine production, and anti-TCR mAb-redirected cytotoxicity. These findings demonstrate that IL-15 and IL-2 are functionally distinct and suggest that IL-15 plays a unique role in the maintenance of the CD8⁺ ß iIEL pool in the absence of Ag stimulation and in the survival and expansion of CD8⁺ ß iIEL upon Ag stimulation.

This article has been cited by other articles:

				Y.-G. Lai, M.-S. Hou, Y.-W. Hsu, C.-L. Chang, Y.-H. Liou, M.-H. Tsai, F. Lee, and N.-S. Liao IL-15 Does Not Affect IEL Development in the Thymus but Regulates Homeostasis of Putative Precursors and Mature CD8{alpha}{alpha}+ IELs in the Intestine J. Immunol., March 15, 2008; 180(6): 3757 - 3765. [Abstract] [Full Text] [PDF]

				H. Robertson, S. Ali, B. J. McDonnell, A. D. Burt, and J. A. Kirby Chronic Renal Allograft Dysfunction: The Role of T Cell-Mediated Tubular Epithelial to Mesenchymal Cell Transition J. Am. Soc. Nephrol., February 1, 2004; 15(2): 390 - 397. [Abstract] [Full Text] [PDF]

				M. Berard, K. Brandt, S. B. Paus, and D. F. Tough IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells J. Immunol., May 15, 2003; 170(10): 5018 - 5026. [Abstract] [Full Text] [PDF]

				N. Kinoshita, T. Hiroi, N. Ohta, S. Fukuyama, E. J. Park, and H. Kiyono Autocrine IL-15 Mediates Intestinal Epithelial Cell Death Via the Activation of Neighboring Intraepithelial NK Cells J. Immunol., December 1, 2002; 169(11): 6187 - 6192. [Abstract] [Full Text] [PDF]

				H.-C. Wang, Q. Zhou, J. Dragoo, and J. R. Klein Most Murine CD8+ Intestinal Intraepithelial Lymphocytes Are Partially But Not Fully Activated T Cells J. Immunol., November 1, 2002; 169(9): 4717 - 4722. [Abstract] [Full Text] [PDF]

				R. Hoontrakoon, H. W. Chu, S. J. Gardai, S. E. Wenzel, P. McDonald, V. A. Fadok, P. M. Henson, and D. L. Bratton Interleukin-15 Inhibits Spontaneous Apoptosis in Human Eosinophils via Autocrine Production of Granulocyte Macrophage-Colony Stimulating Factor and Nuclear Factor-kappa B Activation Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 404 - 412. [Abstract] [Full Text] [PDF]

				T.-S. Wu, J.-M. Lee, Y.-G. Lai, J.-C. Hsu, C.-Y. Tsai, Y.-H. Lee, and N.-S. Liao Reduced Expression of Bcl-2 in CD8+ T Cells Deficient in the IL-15 Receptor {alpha}-Chain J. Immunol., January 15, 2002; 168(2): 705 - 712. [Abstract] [Full Text] [PDF]

				H.-C. Wang and J. R. Klein Multiple Levels of Activation of Murine CD8+ Intraepithelial Lymphocytes Defined by OX40 (CD134) Expression: Effects on Cell-Mediated Cytotoxicity, IFN-{gamma}, and IL-10 Regulation J. Immunol., December 15, 2001; 167(12): 6717 - 6723. [Abstract] [Full Text] [PDF]

				J. Dunne, S. Lynch, C. O'Farrelly, S. Todryk, J. E. Hegarty, C. Feighery, and D. G. Doherty Selective Expansion and Partial Activation of Human NK Cells and NK Receptor-Positive T Cells by IL-2 and IL-15 J. Immunol., September 15, 2001; 167(6): 3129 - 3138. [Abstract] [Full Text] [PDF]

				T. A. Fehniger and M. A. Caligiuri Interleukin 15: biology and relevance to human disease Blood, January 1, 2001; 97(1): 14 - 32. [Full Text] [PDF]

				B. R. Lauwerys, N. Garot, J.-C. Renauld, and F. A. Houssiau Cytokine Production and Killer Activity of NK/T-NK Cells Derived with IL-2, IL-15, or the Combination of IL-12 and IL-18 J. Immunol., August 15, 2000; 165(4): 1847 - 1853. [Abstract] [Full Text] [PDF]

				R. Nishiyama, T. Sakaguchi, T. Kinugasa, X. Gu, R. P. MacDermott, D. K. Podolsky, and H.-C. Reinecker Interleukin-2 Receptor beta Subunit-dependent and -independent Regulation of Intestinal Epithelial Tight Junctions J. Biol. Chem., September 14, 2001; 276(38): 35571 - 35580. [Abstract] [Full Text] [PDF]