In vivo rescue of defective memory CD8+ T cells by cognate helper T cells

Abstract

The magnitude and efficacy of CD8+ T cell memory may notably regress, especially if immune induction occurs in the absence of adequate CD4+ help. This report demonstrates that this CD8+ memory malfunction could be remedied if a source of cognate antigen-recognizing helper cells were provided during recall. The inability of adoptive transfer of memory SIINFEKL-specific CD8 cells to reject tumors was overcome if recipients were primed for ovalbumin-specific helper cell responses. Additionally, animals primed for a SIINFEKL-specific memory response and incapable of rejecting the tumor could regain protective immunity if given helper cells. This pattern of CD8+ T cell functional rescue or reprogramming by helper cell transfer was replicated using a Herpes simplex virus antiviral immunity system. Our results could mean that therapeutic vaccine approaches could be designed to compensate situations that have defective CD8+ T cell function.