Chronic interferon-γ stimulation impairs memory CD8 T cell maintenance

Memory CD8 T cells are long-lived antigen-specific T cells which respond more quickly to, and exhibit better protection from, the same pathogen than naive T cells. Memory CD8 T cells are maintained at a stable size over long periods, but the mechanisms by which their size is maintained remain elusive. Memory CD8 T cells which have been formed in wild-type (WT) mice survive poorly when transferred into MHC class II (MHCII)-deficient hosts as compared to those transferred into WT or other CD4 T cell-deficient hosts, suggesting that other as-yetunknown factors than CD4 T cell-deficiency may account for the defective memory CD8 T cell maintenance in the MHCII-deficient environment. Transcriptome analyses revealed upregulation of interferon (IFN)-inducible genes in memory CD8 T cells in MHCII-deficient hosts relative to those in WT hosts. Consistent with the upregulation of IFN-inducible genes, the levels of IFN-γ, but not type I IFN, were elevated in the plasma of MHCII-deficient mice. Neutralization of IFN-γ restored the numbers of memory CD8 T cells in MHCII-deficient mice, while continuous IFN-γ administration reduced memory CD8 T cell numbers in WT mice. Collectively, these data
indicate that the increased IFN-γ levels in MHCII-deficient mice account for the defective homeostatic maintenance of memory CD8 T cells.