The length of the secondary stimulus controls the magnitude of recall responses by CD4+ T cells (83.10)

Abstract

Abstract The parameters controlling the generation of robust CD4+ T cell recall responses remain poorly defined. In this study we compared recall responses by CD4+ and CD8+ memory T cells following rechallenge. Homologous rechallenge of mice immune to either lymphocytic choriomeningitis virus (LCMV) or Listeria monocytogenes resulted in robust CD8+ T cell recall responses but poor boosting of CD4+ T cell recall responses in the same host. In contrast, heterologous rechallenge with a pathogen sharing only a CD4+ T cell epitope resulted in robust boosting of CD4+ T cell recall responses. Robust CD4+ and CD8+ T cell recall responses were simultaneously induced following rechallenge with peptide-pulsed dendritic cells, ruling out the possibility that the disparity in CD4+ and CD8+ T cell recall responses could be attributed to competition for growth factors or APCs. Instead, CD4+ T cell recall responses were dependant on the duration of the secondary challenge. Increasing the rechallenge dose resulted in more potent boosting of CD4+ T cell recall responses, and artificially limiting the duration of infection following heterologous rechallenge adversely impacted the magnitude of CD4+ T cell, but not CD8+ T cell, recall responses. These findings suggest that rapid pathogen clearance by secondary CTL following homologous rechallenge prevents optimal boosting of CD4+ T cell responses.