Abstract
Memory T cells (Tmem) rapidly mount Ag-specific responses during pathogen reencounter. However, Tmem also respond to inflammatory cues in the absence of an activating TCR signal, a phenomenon termed bystander activation. Although bystander activation was first described over 20 years ago, the physiological relevance and the consequences of T cell bystander activation have only become more evident in recent years. In this review, we discuss the scenarios that trigger CD8 Tmem bystander activation including acute and chronic infections that are either systemic or localized, as well as evidence for bystander CD8 Tmem within tumors and following vaccination. We summarize the possible consequences of bystander activation for the T cell itself, the subsequent immune response, and the host. We highlight when T cell bystander activation appears to benefit or harm the host and briefly discuss our current knowledge gaps regarding regulatory signals that can control bystander activation.
Footnotes
This work was supported by National Institutes of Health Grant R01 AI123323 (to M.P.) and National Cancer Institute Grant 1F99CA245735-01 (to N.J.M.). N.J.M. is a Leslie and Pete Higgins Achievement Rewards for College Scientists Fellow and Dr. Nancy Herrigel-Babienko Memorial Scholar.
Abbreviations used in this article:
- AHA
- acute hepatitis A
- GzmB
- granzyme B
- HAV
- hepatitis A virus
- IAV
- influenza A virus
- NKG2DL
- NKG2D ligand
- RA
- rheumatoid arthritis
- TME
- tumor microenvironment
- Tmem
- memory T cell
- TRM
- resident memory T cell
- YFV
- yellow fever virus.
- Received August 10, 2020.
- Accepted September 11, 2020.
- Copyright © 2021 by The American Association of Immunologists, Inc.
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