We have previously shown that mice challenged with a lethal dose of PR8-OVAI are protected by injection of 4 to 8 × 106 in vitro - generated Tc1 or Tc17 CD8+ effectors. Viral load, lung damage and loss of lung function are all reduced following transfer. Weight loss is reduced and survival increased. We sought here to define the mechanism of this protection. CD8+ effectors exhibit multiple effector activities, perforin-, FasL- and TRAIL- mediated cytotoxicity, secretion of multiple cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-17, IL-21, IL-22, IFN-γ and TNF) and chemokines (CCL3, CCL4, CCL5, CXCL9 and CXCL10). Transfer of CD8+ effectors into recipients, prior to infection, elicits enhanced recruitment of host neutrophils, NK cells, macrophages, and B cells. All of these events have the potential to protect against viral infections. Removal of any one, however, of these potential mechanisms was without effect on protection. Even the simultaneous removal of host T cells, host B cells and host neutrophils combined with the elimination of perforin mediated lytic mechanisms in the donor cells failed to reduce their ability to protect. We conclude that CD8+ effector T cells can protect against the lethal effects of viral infection by means of a large number of redundant mechanisms.
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