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* Université de Lyon, France;
Institut National de la Santé Et de la Recherche Médicale, U851, Lyon, France;
Université Lyon 1, IFR128, France; and
Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, France
Most memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122int memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-
secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122high memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by institutional grants from the Institut National de la Santé Et de la Recherche Médicale, Université Claude Bernard Lyon 1, the Association pour la Recherche contre le Cancer, the Ligue Régionale de Lutte Contre le Cancer, the Région Rhône-Alpes, and the Institut National du Cancer (ACI-63-04). F.M.M.-K. was supported by the Centrafrican government and the Association pour la Recherche contre le Cancer and A.C. and C.-A.C. by the French Ministère de l’Education et de la Recherche.
2 Current address: Université de Lausanne, Department of Biochemistry, Ch. Des Boveresses 155, Epalinges, Switzerland.
3 Current address: Ludwig Institute for Cancer Research, Lausanne Branch, Ch. Des Boveresses 155, Epalinges, Switzerland.
4 Current address: Hammersmith Hospital, Imperial College School of Medicine, Du Cane Road, London, United Kingdom.
5 C.A. and J.M. share co-authorship.
6 Address correspondence and reprint requests to Dr. Jacqueline Marvel, Institut National de la Santé Et de la Recherche Médicale U851, 21 Avenue Tony Garnier, Lyon, France. E-mail address: jacqueline.marvel{at}inserm.fr
7 Abbreviations used in this paper: DC, dendritic cell; PRR, pattern recognition receptor; PAMP, pathogen-associated molecular pattern; DTH, delayed-type hypersensitivity; CHS, contact hypersensitivity; CM, culture medium; BMDC, bone marrow-derived DC; qPCR, quantitative real-time PCR; KLRG1, killer cell lectin-like receptor G1; DNFB, 2,4-dinitrofluorobenzene; PD-1, programmed death-1; TCM, T central memory; TIM, T inflammatory memory; LN, lymph node.
8 The online version of this article contains supplemental material.
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