Generation of cellular immunity to lymphocytic choriomeningitis virus is independent of CD1d1 expression

Abstract

SUMMARYCD1 molecules are cell surface glycoproteins, structurally similar to major histocompatibility complex (MHC) class I molecules. The murine CD1d1 molecule has been shown to be essential for the positive selection of a unique subpopulation of T cells [the natural killer (NK) T cells], as CD1d1-de®cient mice lack NK T cells. These cells have recently been suggested to play an important role in the induction of innate immunity (i.e. NK cells) and the regulation of immune homeostasis. As such, it was asked whether NK T cells were necessary for the generation of cellular immunity to an acute virus infection. In these studies, the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), a classic inducer of NK cells, and its pathogenic variant clone 13 were used. When NK-cell activity was assessed on day 3 post-LCMV infection, surprisingly, it was found that CD1d1-de®cient mice could generate NK-cell activity at wild-type levels. Likewise, LCMV-speci®c cytotoxic T-lymphocyte (CTL) activity in CD1d1-de®cient mice was indistinguishable from that generated in wild-type mice. Additionally, viral titres in the spleen (LCMV Armstrong) and blood (LCMV clone 13) of infected CD1d1-de®cient mice were at comparable levels to those found in wild-type mice, as were virus infection-induced increases in cell surface H-2K b in the spleen. Therefore, these results suggest that the LCMV-induced generation of NK-cell and virus-speci®c CTL activity, as well as viral clearance, are independent of CD1d1 expression.

Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

“…Others have also seen such a reduction in liver NKT cells following treatment of mice with ␣-GalCer (19,43,48) or anti-CD3 (18) and have reported a role for NKT-cell-produced IFN-␥ in the induction of NK cell activity (13,19). In the case of LCMV, we have found that the virus-induced NK cell activity is actually normal in an NKT-cell-deficient environment (i.e., CD1d1-deficient mice) (57), and LCMV infection also resulted in the loss of NKT cells in IFN-␥-deficient mice (Table 1). This suggests that the importance of NKT cells in various infections will be dependent not only on the pathogens, but also the cytokines that they induce.…”

“…Thus, viral clearance has multiple mechanisms by which it can occur and is different depending upon the virus. We have found that even in an NKT-cell-deficient (i.e., CD1d1 knockout mice) environment, the in vivo control of LCMV is comparable to that in wild-type mice (57). Thus, in that model, either the lack of NKT cells is beneficial, by preventing an NKT-cell-mediated cytotoxic response affecting hepatocytes and other tissues, or, alternatively, NKT cells simply play no role in the control of that virus infection.…”

NKT cells: Friend or foe during viral infections?

“…Regardless to the effect of LCMV on iNKT cells, these cells do not seem to be indispensable for innate and CTL responses in the spleen, as Cd1d À/À and WT mice have similar splenic viral loads and LCMV-specific cytotoxic T-cell responses [42]. However, the same team later reported that LCMV infection of Cd1d À/À mice resulted in significantly higher splenocyte production of IL-2, IL-4 and IFN-g than in WT controls [43].…”

Myeloid marker expression on antiviral CD8+ T cells following an acute virus infection

“…Mouse H-2D b tetramers loaded with GP33 and NP366 [14] and conjugated with PE were kindly provided by Dr. Liisa Selin (University of Massachusetts Medical School, Worcester, MA). The labeling procedure and FACS analyses were performed as described previously [28,29]. Samples were analyzed on a FACSCalibur flow cytometer (Becton Dickinson, Mountain View, CA), with 10,000-50,000 events acquired per sample as indicated.…”