The protection against MNV infection in aged mice in the absence of robust generation of anti-MNV antibodies raised the possibility that an important component of the vaccine response is T cell dependent, a hypothesis borne out in adoptive transfer studies. Importantly, the antiviral effector perforin is important in the clearance of MNV from the intestine, suggesting that the cytotoxic T cell response is a key effector mechanism. It is possible that other cell types such as NK cells might also use perforin as a mechanism to control MNV infection. Our data do not rule out a role for IFNc in clearance of MNV infection since NK cells in recipient RAG1-/-mice can make IFNc, but do suggest that T cell derived IFNc plays at most a minor role in effector T cell function in the ileum. This argues that classical CTL assays may be a good surrogate for the development of effective vaccine-generated immune responses to HuNV.