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Programmed death-1 shapes memory phenotype CD8 T cell subsets in a cell-intrinsic manner
Joanna J Charlton1, Ioannis Chatzidakis, Debbie Tsoukatou
1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, GR-70013 Heraklion, Crete, Greece.
Journal of Immunology (Baltimore, Md. : 1950)
|May 21, 2013
Summary
Programmed death-1 (PD-1) regulates memory phenotype CD8 T cells. PD-1 knockout mice show increased effector memory T cells, suggesting PD-1 controls T cell differentiation and homeostasis.
Area of Science:
- Immunology
- Cell Biology
Background:
- Memory phenotype T cells are crucial for immune protection.
- The mechanisms controlling memory T cell homeostasis are not fully understood.
Purpose of the Study:
- To investigate the role of programmed death-1 (PD-1) in regulating memory phenotype CD8 T cell development and homeostasis.
Main Methods:
- Analysis of PD-1 knockout (KO) mice.
- Flow cytometry to identify T cell subsets (T(EM), T(CM)).
- Mixed bone marrow transfer experiments.
- Global transcriptional analysis.
Main Results:
- PD-1 KO mice exhibit accumulation of functional effector memory (T(EM)) CD8 T cells.
- T(EM) cells in PD-1 KO mice show decreased proliferation but increased survival.
- PD-1 deficiency skews naive T cells toward T(EM) phenotype during lymphopenia-induced proliferation.
- PD-1 acts as a checkpoint in the differentiation from central memory (T(CM)) to T(EM) phenotype.
Conclusions:
- PD-1 plays a critical role in regulating the developmental fates and homeostasis of memory phenotype CD8 T cells.
- PD-1 influences the balance between T(CM) and T(EM) cell populations, shaping the overall memory CD8 T cell pool.
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