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Protective CD8 T cell memory is impaired during chronic CD70-driven costimulation.
Klaas P J M van Gisbergen1, Ronald W van Olffen, Josine van Beek
1Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. k.p.vangisbergen@amc.nl
Journal of Immunology (Baltimore, Md. : 1950)
|April 22, 2009
Summary
Constitutive CD70 costimulation drives CD8 T cell exhaustion, impairing memory formation during chronic infections. This deregulation mimics chronic infection pathways, affecting CD8 T cell differentiation.
Area of Science:
- Immunology
- T cell biology
- Infectious disease
Background:
- Chronic infections lead to persistent effector CD8 T cell formation and exhaustion, hindering memory CD8 T cell development.
- Costimulatory molecule CD70 expression remains elevated during chronic infections.
Purpose of the Study:
- To investigate the impact of continuous CD70-driven costimulation on T cell responses.
- To analyze how constitutive CD70 expression affects CD8 T cell differentiation and memory formation.
Main Methods:
- Generation of transgenic mice expressing CD70 specifically on T cells.
- Analysis of CD8 T cell populations and function in response to influenza infection.
- Assessment of primary and secondary immune responses.
Main Results:
- Constitutive CD70 expression promoted CD8 T cell accumulation resembling exhausted effector cells.
- Enhanced primary CD8 T cell responses against influenza were observed.
- Impaired memory CD8 T cell maintenance and protection against secondary influenza challenge occurred.
- No significant effects were noted on effector or memory CD4 T cell populations.
Conclusions:
- Constitutive CD70 expression is sufficient to disrupt normal CD8 T cell differentiation during acute infection, mimicking chronic infection states.
- CD70-driven costimulation dysregulates CD8 T cell fate, promoting exhaustion over memory formation.
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