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Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro
M Pihlgren1, P M Dubois, M Tomkowiak
1Laboratoire de Biologie Moleculaire et Cellulaire de Ecole Normale Superieure Lyon centre National de la Recherche Scientifique Unité Mixte de Recherche, France.
The Journal of Experimental Medicine
|December 1, 1996
Summary
Primed CD8+ T cells exhibit lower activation thresholds than naive cells, indicating enhanced responsiveness crucial for immunological memory. These findings clarify the characteristics of memory CD8+ T cells.
Area of Science:
- Immunology
- Cellular Immunology
- T cell biology
Background:
- The specific characteristics differentiating naive from memory CD8+ T cells, particularly their activation thresholds, remain poorly understood.
- Heterogeneity within primed CD8+ T cell populations complicates the assessment of their activation requirements and roles in memory responses.
Purpose of the Study:
- To investigate the activation thresholds of naive versus primed CD8+ T cells.
- To characterize the phenotype and responsiveness of a homogeneous population of primed CD8+ T cells.
Main Methods:
- Utilized F5 T cell receptor transgenic mice to generate a homogeneous population of primed CD8+ T cells.
- Employed in vivo BrdU labeling to track primed T cells post-immunization.
- Assessed cell surface phenotype (CD44, Ly6C) and responsiveness to secondary peptide challenge.
- Compared in vitro activation thresholds and interleukin 2 receptor alpha chain (CD25) upregulation kinetics between naive and primed CD8+ T cells.
Main Results:
- Primed CD8+ T cells in this model were largely non-cycling, expressing elevated CD44 and Ly6C.
- These primed cells demonstrated sustained responsiveness to secondary peptide challenge.
- In vitro, primed CD8+ T cells activated at 10-50 fold lower peptide concentrations than naive cells.
- Distinct kinetics of interleukin 2 receptor alpha chain upregulation were observed in primed CD8+ T cells.
Conclusions:
- Primed CD8+ T cells possess significantly lower activation thresholds compared to naive CD8+ T cells.
- This heightened responsiveness suggests a critical role for these hyperresponsive CD8+ T cells in establishing and maintaining immunological memory.