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Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro.

Pihlgren M, Dubois PM, Tomkowiak M, Sjögren T, Marvel J - J. Exp. Med. (1996)

Bottom Line: These cells differ in terms of cell cycle status, surface phenotype, and/or effector function.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie Moleculaire et Cellulaire de Ecole Normale Superieure Lyon centre National de la Recherche Scientifique Unité Mixte de Recherche, France.

ABSTRACT
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 2R alpha 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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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 and CD44. The cell size of CD8+ T cells as well  as the expression of CD69 or CD44 by these cells are shown. Results for one naive and two primed mice are shown. (c) The percentage of CD8+ T cells  proliferating in response to peptide challenge was measured by BrdU incorporation. Spleen cells were double stained for BrdU and CD8. The percentage  of BrdU+ and BrdU− CD8+ T cells is given. The total number (×106) of BrdU+CD8+ cells is given in brackets. Results for one representative mouse  out of two are shown.
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Figure 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 and CD44. The cell size of CD8+ T cells as well as the expression of CD69 or CD44 by these cells are shown. Results for one naive and two primed mice are shown. (c) The percentage of CD8+ T cells proliferating in response to peptide challenge was measured by BrdU incorporation. Spleen cells were double stained for BrdU and CD8. The percentage of BrdU+ and BrdU− CD8+ T cells is given. The total number (×106) of BrdU+CD8+ cells is given in brackets. Results for one representative mouse out of two are shown.

Mentions: Because in some systems peptide challenge can also lead to anergy (22), we studied the in vivo response to peptide of primed CD8+ T lymphocytes. Primed and naive thymectomized mice were challenged with peptide as described in Fig. 5 a, and the changes of surface phenotype as well as the proliferation of CD8+ T cells were measured.


Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro.

Pihlgren M, Dubois PM, Tomkowiak M, Sjögren T, Marvel J - J. Exp. Med. (1996)

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 and CD44. The cell size of CD8+ T cells as well  as the expression of CD69 or CD44 by these cells are shown. Results for one naive and two primed mice are shown. (c) The percentage of CD8+ T cells  proliferating in response to peptide challenge was measured by BrdU incorporation. Spleen cells were double stained for BrdU and CD8. The percentage  of BrdU+ and BrdU− CD8+ T cells is given. The total number (×106) of BrdU+CD8+ cells is given in brackets. Results for one representative mouse  out of two are shown.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196370&req=5

Figure 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 and CD44. The cell size of CD8+ T cells as well as the expression of CD69 or CD44 by these cells are shown. Results for one naive and two primed mice are shown. (c) The percentage of CD8+ T cells proliferating in response to peptide challenge was measured by BrdU incorporation. Spleen cells were double stained for BrdU and CD8. The percentage of BrdU+ and BrdU− CD8+ T cells is given. The total number (×106) of BrdU+CD8+ cells is given in brackets. Results for one representative mouse out of two are shown.
Mentions: Because in some systems peptide challenge can also lead to anergy (22), we studied the in vivo response to peptide of primed CD8+ T lymphocytes. Primed and naive thymectomized mice were challenged with peptide as described in Fig. 5 a, and the changes of surface phenotype as well as the proliferation of CD8+ T cells were measured.

Bottom Line: These cells differ in terms of cell cycle status, surface phenotype, and/or effector function.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biologie Moleculaire et Cellulaire de Ecole Normale Superieure Lyon centre National de la Recherche Scientifique Unité Mixte de Recherche, France.

ABSTRACT
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 2R alpha 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.

Show MeSH