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Departments of
*
Microbiology and Immunology and
Oral and Maxillofacial Surgery, Tokyo Women’s Medical University School of Medicine, and
Institute of Laboratory Animals, Tokyo Women’s Medical University, Tokyo, Japan;
Interdisciplinary Research Center of Autoimmune Diseases, Department of Medical Sciences, A. Avogadro University of Eastern Piedmont, Novara, Italy; and
¶ Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
We found a tight correlation among the levels of H4/inducible costimulator (ICOS) expression, IL-4 production, and GATA-3 induction, using activated CD4+ T cells obtained from six different murine strains. BALB/c-activated CD4+ T cells expressed 
10-fold more H4/ICOS on their surfaces and produced 10-fold more IL-4 upon restimulation than C57BL/6-activated CD4+ T cells. BALB/c naive CD4+ T cells were shown to produce much higher amounts of IL-2 and IL-4 upon primary stimulation than C57BL/6 naive CD4+ T cells. Neutralization of IL-4 with mAbs in culture of BALB/c naive CD4+ T cells strongly down-regulated both H4/ICOS expression on activated CD4+ T cells and IL-4 production upon subsequent restimulation. Conversely, exogenous IL-4 added to the culture of BALB/c or C57BL/6 naive CD4+ T cells up-regulated H4/ICOS expression and IL-4 production upon restimulation. In addition, retroviral expression of GATA-3 during the stimulation of naive CD4+ T cells from C57BL/6 or IL-4-/- mice increased H4/ICOS expression on activated CD4+ T cells. A similar effect of IL-2 in the primary culture of BALB/c naive CD4+ T cells appeared to be mediated by IL-4, the production of which was regulated by IL-2. These data suggest that IL-4 induced by IL-2 is critical to the maintenance of high H4/ICOS expression on BALB/c-activated CD4+ T cells.
This article has been cited by other articles:
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  M. Watanabe, Y. Takagi, M. Kotani, Y. Hara, A. Inamine, K. Hayashi, S. Ogawa, K. Takeda, K. Tanabe, and R. Abe Down-Regulation of ICOS Ligand by Interaction with ICOS Functions as a Regulatory Mechanism for Immune Responses J. Immunol., April 15, 2008; 180(8): 5222 - 5234. [Abstract] [Full Text] [PDF]
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 J. M. Rojo, E. Pini, G. Ojeda, R. Bello, C. Dong, R. A. Flavell, U. Dianzani, and P. Portoles CD4+ICOS+ T lymphocytes inhibit T cell activation 'in vitro' and attenuate autoimmune encephalitis 'in vivo' Int. Immunol., April 1, 2008; 20(4): 577 - 589. [Abstract] [Full Text] [PDF]
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 A. H.-M. Tan, S. Y.-P. Goh, S.-C. Wong, and K.-P. Lam T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3 J. Biol. Chem., January 4, 2008; 283(1): 128 - 136. [Abstract] [Full Text] [PDF]
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J. Yagi, Y. Arimura, H. Takatori, H. Nakajima, I. Iwamoto, and T. Uchiyama Genetic background influences Th cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4+ T cells Int. Immunol., December 1, 2006; 18(12): 1681 - 1690. [Abstract] [Full Text] [PDF]
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M. F. Quiroga, V. Pasquinelli, G. J. Martinez, J. O. Jurado, L. C. Zorrilla, R. M. Musella, E. Abbate, P. A. Sieling, and V. E. Garcia Inducible Costimulator: A Modulator of IFN-{gamma} Production in Human Tuberculosis J. Immunol., May 15, 2006; 176(10): 5965 - 5974. [Abstract] [Full Text] [PDF]
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 J.-H. Yang, J. Zhang, Q. Cai, D.-B. Zhao, J. Wang, P.-E. Guo, L. Liu, X.-H. Han, and Q. Shen Expression and function of inducible costimulator on peripheral blood T cells in patients with systemic lupus erythematosus Rheumatology, October 1, 2005; 44(10): 1245 - 1254. [Abstract] [Full Text] [PDF]
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M. E. A. T. van Berkel, E. H. R. Schrijver, F. M. A. Hofhuis, A. H. Sharpe, A. J. Coyle, C. P. Broeren, K. Tesselaar, and M. A. Oosterwegel ICOS Contributes to T Cell Expansion in CTLA-4 Deficient Mice J. Immunol., July 1, 2005; 175(1): 182 - 188. [Abstract] [Full Text] [PDF]
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L. Wassink, P. L. Vieira, H. H. Smits, G. A. Kingsbury, A. J. Coyle, M. L. Kapsenberg, and E. A. Wierenga ICOS Expression by Activated Human Th Cells Is Enhanced by IL-12 and IL-23: Increased ICOS Expression Enhances the Effector Function of Both Th1 and Th2 Cells J. Immunol., August 1, 2004; 173(3): 1779 - 1786. [Abstract] [Full Text] [PDF]
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B. Greve, L. Vijayakrishnan, A. Kubal, R. A. Sobel, L. B. Peterson, L. S. Wicker, and V. K. Kuchroo The Diabetes Susceptibility Locus Idd5.1 on Mouse Chromosome 1 Regulates ICOS Expression and Modulates Murine Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2004; 173(1): 157 - 163. [Abstract] [Full Text] [PDF]
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Y. Arimura, F. Shiroki, S. Kuwahara, H. Kato, U. Dianzani, T. Uchiyama, and J. Yagi Akt Is a Neutral Amplifier for Th Cell Differentiation J. Biol. Chem., March 19, 2004; 279(12): 11408 - 11416. [Abstract] [Full Text] [PDF]
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