unimmunized mice as novel immunomodulator of IFN-g-dependent type 1 immunity

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-2Rb, CD62L and CCR7 cell-surface molecules. Among CD44 high CD8 + so-called memory CD8 + T cell population, ASGM1 + CD44 high CD8 + TCMT, but not ASGM1 � CD44 high CD8 + memory T cells, produced IFN-g by stimulation with anti-CD3 mAb. The physiological significance of ASGM1 + CD8 + TCMT as early source of IFN-g was also demonstrated in vivo. Namely, intravenous injection of anti-CD3 mAb (2 mg) resulted in early activation of IFN-gproducing ASGM1 + CD8 + TCMT cells as well as NKT and NK cells. Unexpectedly, however, few IFN-gproducing CD4 + T cells were detected until 4 h after anti-CD3 mAb administration. Thus, ASGM1 + CD8 + TCMT were demonstrated to be early IFN-g 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-g-producing Th1 cells in vitro. Finally, we found that Th1prone 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-g 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.