CD4 T cell derived IFN-gamma protects from lethal encephalomyelitis by inhibiting neutrophil infiltration independent of IL-17 (45.6)

Abstract

Abstract Immunodeficient SCID recipients of virus-primed memory CD4 T cells survive CNS infection by neurotropic coronavirus (JHMV), whereas IFN-γ deficient (GKO) donor CD4 T cells substantially increase morbidity. Control of virus replication and demyelination are similar in both recipients compared to uncontrolled replication without demyelination in non-treated mice. However, distinct from wt CD4 T cell recipients, GKO recipients exhibit massive CNS neutrophil infiltration, prominent CD4 T cell localization to grey matter, and detection of IL-17 mRNA. To determine the relative role of IFN-γ, IL-17 and neutrophils in disease severity, equal populations of wt and GKO CD4 T cells were co-transferred to SCID mice. Despite the vast abundance of GKO versus wt CD4 T cells accumulating in the CNS at 8 days p.i. (80 vs 20 %), disease severity and survival was similar to protected recipients of wt CD4 T cells. Furthermore, the minor population of wt CD4 T cells in mixed recipients resulted in decreased CNS neutrophil infiltration, consistent with modestly elevated IFN-γ and reduced neutrophil-attracting chemokines. However, wt CD4 T cells did not reduce CNS IL-17 mRNA levels in recipients of mixed relative to GKO donor cells. The data suggest that IFN-γ dominates over IL-17 in controlling excessive neutrophil recruitment and thus protecting JHMV infected SCID recipients from premature death.