Memory T cell stability in the wake of heterologous viral infections (105.35)

Abstract

Abstract CD8 T cell memory is generally stable but can be reduced by heterologous infections. CD44hi CD8 and CD4 T cells undergo attrition early during infection with type I IFN-inducing pathogens or after exposure to toll receptor agonists. This attrition coincides with the early reduction of bona fide virus-specific CD8 and CD4 memory T cells and can explain the long-term loss in memory T cells that occurs after heterologous infection. An increase in the percentage of apoptotic cells was detected by TUNEL assay in both CD44hi CD8 and CD44hi CD4 T cells at day 3 post-infection with lymphocytic choriomeningitis virus (LCMV), a strong type I IFN inducer. Infection with LCMV significantly reduced vaccinia (VV)-specific CD8 memory T cells, which were further reduced by heterologous infection with murine cytomegalovirus (MCMV). MCMV also reduced LCMV-specific CD8 and CD4 memory T cells, but LCMV memory was not further eroded by persistent MCMV infection over a 48-week period, even though MCMV-specific memory cells increased in number due to memory inflation. This argued that the early IFN-dependent attrition had a greater effect on memory loss than did competition later on by inflating memory cells. A caveat, however, is that MCMV memory inflation was somewhat impaired by a prior LCMV infection, possibly due to reduced latent MCMV load caused by heterologous immunity. These results illustrate the dynamic nature of T cell memory in the wake of acute and persistent viral infections.