Long-term loss of canonical NKT cells following an acute virus infection.

NKT cell activation plays an important role in regulating innate and adaptive immunity during infection. We have previously found that there is a dramatic reduction in the NKT cell population on day 3 after an acute lymphocytic choriomeningitis virus (LCMV) infection. In this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the TCR. Concomitant with the decrease in NKT cells was an increase in the percentage of Annexin V(+) NKT cells that remained in vivo, suggesting that the reduction in NKT cells at these late stages post-infection occurred by activation-induced cell death. Interestingly, APC from LCMV-infected mice could activate NKT cells in vitro at higher levels than those from uninfected mice and was concomitant with an increase in apoptosis in NKT cells. However, this could not be blocked by mAb to murine CD1d, and APC from LCMV-infected (but not uninfected) CD1d1-deficient mice could also stimulate NKT cells. Collectively, our data suggest that the activation and subsequent long-term loss of NKT cells is a normal component of the host's antiviral immune response, and this occurs in a CD1d-independent manner.