T-Cell Clones Expressing Different T-Cell Receptors Accumulate in the Brains of Dying and Surviving Mice After Peripheral Infection with Far Eastern Strain of Tick-Borne Encephalitis Virus

Abstract

Tick-borne encephalitis virus (TBEV), a representative acute central nervous system disease-inducible virus, is known to elicit dose-independent mortality in a mouse model. We previously reported that subcutaneous infection with a wide range of TBEV Oshima strain challenge doses (10(2)-10(6) PFU) produced an approximately 50% mortality rate. However, the factors playing critical roles in mortality and severity remain unclear. In this study, we distinguished surviving and dying mice by their degree of weight loss after TBEV infection, and investigated qualitative differences in brain-infiltrating T cells between each group by analyzing T-cell receptor (TCR) repertoire and complementary determining region 3 (CDR3) sequences. TCR repertoire analysis revealed that the expression levels of VA8-1, VA15-1, and VB8-2 families were increased in brains derived from both surviving and dying mice. CDR3 amino acid sequence characteristics differed between each group. In dying mice, high frequencies of VA15-1/AJ12 and VB8-2/BJ1.1 gene usage were observed. While in surviving mice, high frequencies of VA8-1/AJ15 or VA8-1/AJ23 gene usage were observed. VB8-2/BJ2.7 gene usage and short CDR3 were observed frequently in both surviving and dying mice. However, no differences in T-cell activation markers and apoptosis-related genes were observed between these groups using quantitative real-time PCR analysis. These results suggest that TBEV-infection severity may be involved in antigen specificity, but not in the number or activation level of brain-infiltrating T cells.