HSV1 induced encephalitis in susceptible mice such as 129 and BALB/c mice is characterized by CNS inflammation associated with pathogenic Ly6Chigh macrophages and neutrophils. Mortality in this model correlates with degranulation by these cells rather than virus mediated cytopathology. IVIG, composed of pooled human IgG protects these mice by induction of regulatory CD4 T cells including IL-10 secreting Tregs and Tr1 cells secreting IL-10 and IFNγ. Surprisingly, IFNγ has an anti-inflammatory role in this model as infection of IFNγKO mice results in severe early morbidity and mortality associated with unabated CNS inflammation by neutrophils and Ly6Chigh monocytes suggesting that IFNγ is critical in the control of expansion of these cells. Interestingly, IVIG cannot protect IFNγKO mice despite control of infectious virus but not CNS inflammation typified by the inflammatory Ly6Chigh macrophages, indicating that IFNγ is crucial to IVIG’s anti-inflammatory activities. Adoptive transfer of T cells subsets from either WT or IFNγKO mice into Rag recipients reinforced the importance of IFNγ on CNS inflammation. Furthermore, IFNγ appears to have a role in the IVIG induced expansion of Tregs while in the absence of IFNγ, there was an increase in γδ T cells secreting IL-17, which may contribute to the early unmitigated expansion of the neutrophils and monocytes. IFNγ related effects on CEACAM1a and iNOS on monocytes, on Tregs, and the cell subset that secretes IFNγ will be discussed.
- Copyright © 2011 by The American Association of Immunologists, Inc.