αβ and γδ T-cell networks and their roles in natural resistance to viral infections

Abstract

Both αβ and γδ T-cell populations and natural killer (NK) cells include cytotoxic, interferon (IFN)-γ-producing lymphocytes that actively respond to viral infections. We show here that all three populations can provide 'natural resistance' to viruses very early in infection and describe how the T-cell populations are modulated to provide this function. γδ T cells were shown to play a role in controlling vaccinia virus (VV) infections, as VV grew to much higher titers in γδ T-cell knockout mice than in normal mice 3-4 days post-infection. Our studies of the αβ T-cell responses to viruses revealed an interactive network of T cells that is modulated substantially during systemic infections. There is an induction phase associated with a massive virus-specific CD8 T-cell response, an apoptosis phase during which the T cells become sensitized to activation-induced cell death (AICD), a silencing phase, during which the T-cell number and activation state is reduced, and, finally a memory phase associated with the very stable preservation of virus-specific memory cytotoxic T-lymphocyte precursors (pCTL). Infection of mice immune to one virus with a heterologous virus leads to a selective expansion of memory CTL cross-reacting between the two viruses, but, after homeostasis is again established, there is a quantitative reduction and qualitative alteration of memory to the first virus. Our results suggest that memory αβ T cells cross-reactive between heterologous viruses mediate both immunopathology and protective immunity at early stages of the second virus infection. Thus, memory αβ T cells can, like γδ T cells and NK cells, provide natural immunity to viral infections.