A unique mechanism for innate cytokine promotion of T cell responses to viral infections

GC Pien, KB Nguyen, L Malmgaard… - The Journal of …, 2002 - journals.aai.org
GC Pien, KB Nguyen, L Malmgaard, AR Satoskar, CA Biron
The Journal of Immunology, 2002journals.aai.org
The kinetics of CD8 T cell IFN-γ responses as they occur in situ are defined here during
lymphocytic choriomeningitis virus (LCMV) infections, and a unique mechanism for the
innate cytokines IFN-αβ and IL-18 in promoting these responses is defined. Infections of
mice with Armstrong or WE strains of LCMV induced an unexpectedly early day 4 IFN-γ
response detectable in serum samples and spleen and liver homogenates. Production of
IFN-γ was MHC class I/CD8 dependent, but did not require IL-12, NK cells, TCR-γδ T cells …
Abstract
The kinetics of CD8 T cell IFN-γ responses as they occur in situ are defined here during lymphocytic choriomeningitis virus (LCMV) infections, and a unique mechanism for the innate cytokines IFN-αβ and IL-18 in promoting these responses is defined. Infections of mice with Armstrong or WE strains of LCMV induced an unexpectedly early day 4 IFN-γ response detectable in serum samples and spleen and liver homogenates. Production of IFN-γ was MHC class I/CD8 dependent, but did not require IL-12, NK cells, TCR-γδ T cells, MHC class II, or CD4 T cells. Peak response required specific Ag recognition, as administration of antagonist peptide partially impaired day 4 IFN-γ induction, and viral peptide stimulation enhanced CD8 T cell IFN-γ expression in culture. The IFN-γ response was associated with IL-18 and IFN-αβ expression. Furthermore, both factors augmented peptide-driven IFN-γ production in culture, and mice lacking IL-18 or IFN-αβ functions had reduced day 4 IFN-γ. Collectively, these results demonstrate that during viral infections, there is a dramatic in vivo CD8 T cell response preceding maximal expansion of these cells, and that the mechanism supporting this response is dependent on endogenous innate cytokines. Because stimulation by microbial products is linked to innate cytokine expression, the studies also suggest a pathway for precisely limiting T cell functions to times of need.
journals.aai.org