Strain differences in CD8 T cell expansion revealed in vivo during LCMV infection and ex vivo by TCR stimulation (VIR6P.1176)

Abstract

Abstract Lymphocytic choriomeningitis virus (LCMV) infection of C57BL6 (B6) mice induces dramatic virus-specific CD8 T cell expansion. Comparison of B6 and 129-Sve (129) mouse strain responses demonstrated that the magnitude of total LCMV-specific CD8 T cell expansion was much lower in the 129 mice. The difference occurred even though viral titers and proportions of CD8 T cells specific for the three immunodominant epitopes of LCMV were similar. A higher type 1 IFN response was associated with the enhanced expansion in the B6 mice, and the responding CD8 T cells in B6 as compared to 129 mice had elevated levels of the signal transducer and activator of transcription (STAT) 4 but lower levels of the STAT1 molecule used to mediate inhibition of proliferation. The magnitude of the response was significantly diminished in B6 but not 129 mice genetically altered to block in IFN responsiveness, i.e. IFN receptor or STAT1 deficient, such that overall CD8 T cell expansion was now similar in both strains. Culture studies with purified cells demonstrated that in comparison to B6, 129 CD8 T cells had poor proliferative potential when stimulated through the TCR. Thus, intrinsic mechanisms linked to genetic differences regulate the magnitude of CD8 T cell proliferation. The data suggest that these differences have consequences for type 1 IFN requirements in shaping the magnitude of the response and overall immunity to viral infections. Supported by the National Institutes of Health, USA.