AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-γ-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-2Rβ, 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-γ by stimulation with anti-CD3 mAb. The physiological significance of ASGM1+CD8+ TCMT as early source of IFN-γ was also demonstrated in vivo. Namely, intravenous injection of anti-CD3 mAb (2 μg) resulted in early activation of IFN-γ-producing ASGM1+CD8+ TCMT cells as well as NKT and NK cells. Unexpectedly, however, few IFN-γ-producing CD4+ T cells were detected until 4 h after anti-CD3 mAb administration. Thus, ASGM1+CD8+ TCMT were demonstrated to be early IFN-γ 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-γ-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-γ 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. [ABSTRACT FROM AUTHOR]