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The Ugly Duckling Turned to Swan: A Change in Perception of Bystander-Activated Memory CD8 T Cells
Nicholas J Maurice1,2, Alexis K Taber1, Martin Prlic3,4,5
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
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.
Insights
Memory T cells (Tmem) can activate without direct antigen (Ag) stimulation, a process known as bystander activation. This review explores triggers, consequences, and host impact of Tmem bystander activation.
Area of Science:
- Immunology
- Cellular Biology
- Infectious Disease
Background:
- Memory T cells (Tmem) are crucial for rapid immune responses upon pathogen reencounter.
- Tmem can activate through inflammatory signals without direct T cell receptor (TCR) signaling, termed bystander activation.
- The physiological significance of bystander activation has gained recent attention.
Purpose of the Study:
- To review scenarios triggering CD8 Tmem bystander activation.
- To summarize the consequences of bystander activation for T cells, immune responses, and the host.
- To highlight beneficial and detrimental effects of bystander activation and identify knowledge gaps.
Main Methods:
- Literature review of studies on Tmem bystander activation.
- Analysis of triggers across various infection models (acute, chronic, systemic, localized).
- Examination of bystander activation in tumor microenvironments and post-vaccination.
Main Results:
- Bystander activation occurs in diverse conditions, including infections, tumors, and vaccination.
- Consequences vary, impacting T cell fate, subsequent immune responses, and overall host outcome.
- The net effect (beneficial or harmful) depends on context.
Conclusions:
- Bystander activation is a significant immunological phenomenon with complex consequences.
- Understanding regulatory signals controlling bystander activation is critical.
- Further research is needed to fully elucidate its role in health and disease.
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