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In Vivo Assay for Detection of Antigen-specific T-cell Cytolytic Function Using a Vaccination Model
Published on: November 28, 2017
Cutting edge: rapid in vivo killing by memory CD8 T cells
Daniel L Barber1, E John Wherry, Rafi Ahmed
1Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 21, 2003
Summary
Virus-specific memory CD8 T cells exhibit rapid cytotoxic activity in vivo, quickly eliminating target cells upon antigen re-exposure. These memory cells are highly efficient killers, comparable to effector cells, challenging previous assumptions.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Cytotoxic CD8 T cells are crucial for viral clearance.
- The in vivo cytotoxic function of memory CD8 T cells is not fully understood.
- Previous studies suggested limited in vitro cytotoxic capacity of resting memory CD8 T cells.
Purpose of the Study:
- To investigate and compare the in vivo cytotoxic activity of effector and memory CD8 T cells.
- To elucidate the mechanisms and kinetics of target cell elimination by CD8 T cells.
- To assess the efficiency of memory CD8 T cells as cytotoxic effectors in a viral infection model.
Main Methods:
- Induction of acute lymphocytic choriomeningitis virus (LCMV) infection in mice.
- Adoptive transfer of effector and memory CD8 T cells into recipient mice.
- Real-time monitoring of target cell elimination in vivo.
- Perforin-dependent cytotoxicity assays.
- Analysis of CD62L expression on memory CD8 T cells.
Main Results:
- Effector CD8 T cells demonstrated rapid, perforin-dependent killing of target cells within 15 minutes.
- Both CD62L(high) and CD62L(low) memory CD8 T cells rapidly eliminated target cells in vivo within 1-4 hours.
- On a per-cell basis, memory CD8 T cells showed cytotoxic efficiency only slightly lower than effector cells.
- In vivo killing by memory CD8 T cells was significantly more potent than suggested by in vitro assays.
Conclusions:
- Virus-specific memory CD8 T cells possess potent and rapid in vivo cytotoxic capabilities.
- Memory CD8 T cells can quickly regain effector function upon antigen re-encounter.
- These findings highlight the underestimated in vivo killer efficiency of memory CD8 T cells, crucial for secondary immune responses.
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