CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection
Yu-Jung Lu,
Palmira Barreira-Silva,
Shayla Boyce,
Jennifer Powers,
Kelly Cavallo,
Samuel M. Behar
Affiliations
Yu-Jung Lu
Immunology and Microbiology Program, Graduate School of Biomedical Science, University of Massachusetts Medical School, Worcester, MA, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
Palmira Barreira-Silva
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal
Shayla Boyce
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
Jennifer Powers
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
Kelly Cavallo
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
Samuel M. Behar
Immunology and Microbiology Program, Graduate School of Biomedical Science, University of Massachusetts Medical School, Worcester, MA, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA; Corresponding author
Summary: CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.
