Memory CD8+ T cells deficient in IFN-γ protect from a lethal viral disease (105.3)

Abstract

Abstract Ectromelia virus (ECTV), the causative agent of mousepox, is a lethal mouse pathogen of the Orthopoxvirus genus, which also includes variola virus. C57Bl/6 (B6) mice are resistant to ECTV infection while mice such as DBA2/J are susceptible. B6.D2-D6 mice, a B6 congenic strain with the NK complex from DBA2/J are sensitive to ECTV and can be protected by adoptive transfer of memory CD8+ T cells (MTCD8+) from convalescent mice. To ascertain the role of IFNγ in MTCD8+ mediated protection, we transferred MTCD8+ from IFNγ-/- mice (Mγ-/-) into B6.D2-D6 mice and challenged them with ECTV. All naïve CD8+ (NB6) recipients died and all recipients of memory B6 CD8+ (MB6) or Mγ-/- recipients survived. Seven dpi, MB6 and Mγ-/- recipients had significantly less liver damage and virus titers in the spleen and liver than NB6 recipients. This demonstrates that MTCD8+ do not have to produce IFNγ to protect from a viral disease. Of interest, we also found that donor virus-specific cells promoted an endogenous virus-specific TCD8+ response in the spleens and livers of recipients. Next we determined if IFNγ was necessary when MTCD8+ cells were present by transferring MB6 or Mγ-/- CD8+ into IFNγ-/- mice. All NB6 and Mγ-/- recipients succumbed to mousepox while all recipients of MB6 recipients survived. Thus, IFNγ is required for resistance to mousepox but can be produced in sufficient quantities for protection by MTCD8+ or other non-memory cells, probably NK cells or primary T cell effectors.