The role of CD4 T cell help in restoring function of exhausted CD8 T cells during chronic infection

Abstract

Exhaustion of CD8 T cell function is a hallmark of chronic viral infections. Although much advance has been made in understanding the mechanisms mediating this dysfunction, little is known about the functional role of CD4 T cell help in this process. In the current study we investigated the effect newly primed antigen specific CD4 T cells may have on CD8 T cell exhaustion and disease outcome in the murine model of chronic viral infection LCMV Clone‐13. We show that adoptive transfer of monoclonal CD4 T cells during the late stages of an ongoing chronic infection can potentially restore function of virus specific CD8 T cells and lead to reduced viral levels. Furthermore, we demonstrate that blocking the PD‐1 (Programmed Death Recptor‐1) inhibitory pathway following the CD4 T cell transfer results in a synergistic effect in terms of both functional rescue of CD8 T cells and viral control. Our data provides new evidence that delivery of CD4 T cell help during ongoing chronic infection may lead to restoration of CD8 T cell function and allow favorable disease outcome.Funding for this work is through NIH grants to R. Ahmed.