The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1996/12/2141/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2141-2152

Articles

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

Maria Pihlgren, Patrice M. Dubois, Martine Tomkowiak, Tove Sjögren, and Jacqueline Marvel

From the Immunologie Cellulaire, Laboratoire de Biologie Moleculaire et Cellulaire de Ecole Normale Superieure Lyon centre National de la Recherche Scientifique Unité Mixte de Recherche, 69364 LYON cedex 07, France

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.

Address correspondence to Jacqueline Marvel, Immunologie Cellulaire, LBMC de L'ENS Lyon CNRS UMR49, 46 Allée d'Italie, 69364 Lyon cedex 07, France.

M. Pihlgren and P. Dubois are supported by fellowships from the Ligue Nationale Contre le Cancer and the Association Française contre les Myopathies, respectively. This work was supported by institutional grants from the Centre National de la Recherche Scientifique and Ministere de l'éducation et de la Recherche and by additional support from the Association pour la Recherche sur le Cancer, Association Française Contre les Myopathies, and the Comité Départemental de la Ligue Nationale Française contre le Cancer.


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