The viral context instructs the redundancy of costimulatory pathways in driving CD8(+) T cell expansion

Elife. 2015 Aug 11;4:e07486. doi: 10.7554/eLife.07486.

Abstract

Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8(+) T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by lymphocytic choriomeningitis virus (LCMV), CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8(+) T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e., CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8(+) T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8(+) T cell responses.

Keywords: T cells; costimulation; immunology; infectious disease; microbiology; mouse; viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice, Inbred C57BL
  • Muromegalovirus / immunology*

Substances

  • Intercellular Signaling Peptides and Proteins

Grant support

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.