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J Exp Med. 1996 December 1; 184(6): 2141–2152.
PMCID: PMC2196370

Resting Memory CD8+ T Cells are Hyperreactive to Antigenic Challenge In Vitro


The characteristics of CD8+ T cells responsible for memory responses are still largely unknown. Particularly, it has not been determined whether different activation thresholds distinguish naive from memory CD8+ T cell populations. In most experimental systems, heterogeneous populations of primed CD8+ T cells can be identified in vivo after immunization. These cells differ in terms of cell cycle status, surface phenotype, and/or effector function. This heterogeneity has made it difficult to assess the activation threshold and the relative role of these subpopulations in memory responses. In this study we have used F5 T cell receptor transgenic mice to generate a homogeneous population of primed CD8+ T cells. In the F5 transgenic mice, peptide injection in vivo leads to activation of most peripheral CD8+ T cells. In vivo BrdU labeling has been used to follow primed T cells over time periods spanning several weeks after peptide immunization. Our results show that the majority of primed CD8+ T cells generated in this system are not cycling and express increased levels of CD44 and Ly6C. These cells remain responsive to secondary peptide challenge in vivo as evidenced by short term upregulation of activation markers such as CD69 and CD44. The activation thresholds of naive and primed CD8+ T cells were compared in vitro. We found that CD8+ T cells from primed mice are activated by peptide concentrations 10–50-fold lower than naive mice. In addition, the kinetics of interleukin 2Rα chain upregulation by primed CD8+ T cells differ from naive CD8+ T cells. These primed hyperresponsive CD8+ T cells might play an important role in the memory response.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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Figures and Tables

Figure 1
In vivo BrdU incorporation by transgenic CD8+ T cells after peptide stimulation. Thymectomized and euthymic mice were either immunized with 50 nmol peptide on day 0 (Activated) or received only PBS (Naive). BrdU was given in the drinking water ...
Figure 2Figure 2
Primed CD8+ T cells are long lived. The maintenance of BrdU labeled CD8 T cells was measured at different times after peptide stimulation and BrdU labeling. Thymectomized or euthymic mice were either immunized with 50 nmol peptide on day 0 ...
Figure 3Figure 3
Surface phenotype of primed, naive and recently activated CD8+ T cells. The expression of CD8, Vβ11, CD3, CD69, IL-2Rα, IL-2Rβ, IL-2Rγ, ICAM-1, LFA-1, CD45RA, CD45RB, l-selectin, Fas, and CD5 by naive, activated, ...
Figure 4Figure 4
Expression of Ly6C and CD44 by naive, activated, or primed CD8+ T cells. (a) Spleen cells from thymectomized mice primed 5 wk earlier or from naive thymectomized mice and from euthymic mice primed 1 d earlier (activated) or from naive euthymic ...
Figure 5Figure 5Figure 5
In vivo primed CD8+ T cells are responsive to secondary challenge with peptide. (a) Experimental plan of the in vivo CD8+ T cells restimulation. (b) 1 d after peptide stimulation, spleen cells were double stained for CD8 and CD69 or CD8 ...
Figure 6
In vitro proliferative responses of CD8 T cells from primed and naive thymectomized mice. (a) 5 × 104 spleen cells were activated with different concentrations of peptide in the presence or absence of IL-2 as described in Materials and Methods. ...
Figure 7
Expression of IL-2Rα on naive and primed CD8+ T cells after activation with peptide in vitro. 106 spleen cells were activated with 1 nM peptide in the presence or absence of 2.5% IL-2. Expression of IL-2Rα by CD8+ T ...

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