International Immunology Advance Access originally published online on January 17, 2007
International Immunology 2007 19(3):249-256; doi:10.1093/intimm/dxl140
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AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-
-dependent type 1 immunity
1 Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
2 Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo 001-0021, Japan
3 Division of ROYCE' Health Bioscience, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
Correspondence to: T. Nishimura; E-mail: tak24{at}igm.hokudai.ac.jp
In unimmunized specific pathogen-free mice, there are unique memory-type CD8+ T cell populations expressing asialoGM1 (ASGM1). These cells were classified into central memory-type T cells (TCMT) judging from their expression profile of CD44, IL-2Rß, CD62L and CCR7 cell-surface molecules. Among CD44highCD8+ so-called memory CD8+ T cell population, ASGM1+CD44highCD8+ TCMT, but not ASGM1–CD44highCD8+ memory T cells, produced IFN-
by stimulation with anti-CD3 mAb. The physiological significance of ASGM1+CD8+ TCMT as early source of IFN- was also demonstrated in vivo. Namely, intravenous injection of anti-CD3 mAb (2 µg) resulted in early activation of IFN--producing ASGM1+CD8+ TCMT cells as well as NKT and NK cells. Unexpectedly, however, few IFN--producing CD4+ T cells were detected until 4 h after anti-CD3 mAb administration. Thus, ASGM1+CD8+ TCMT were demonstrated to be early IFN- producer, which may be crucial for Th1-dependent cellular immunity. Indeed, co-culture of naive CD4+ T cells with ASGM1+CD8+ TCMT but not ASGM1–CD8+ T cells caused a great acceleration of IFN--producing Th1 cells in vitro. Finally, we found that Th1-prone C57BL/6 mice possessed higher percentage (10%) of ASGM1+CD8+ TCMT in CD8+ T cells compared with that (3%) of Th2-prone BALB/c mice. Moreover, ASGM1+CD8+ TCMT derived from C57BL/6 mice produced higher levels of IFN- compared with those from BALB/c mice. Thus, ASGM1+CD8+ TCMT, whose differentiation in vivo is genetically controlled, appear to play a critical role in the control of type 1 immunity, which is essential for therapy of tumors and infectious diseases.
Keywords: genetic differences, IFN--producing CTLs, immunoregulatory cells, Th1 commitment
Transmitting editor: T. Hamaoka
Received 14 October 2006, accepted 13 December 2006.
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