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Cutting Edge: Enhanced IL-2 Signaling Can Convert Self-Specific T Cell Response from Tolerance to Autoimmunity¹

Jason Waithman^2,*, Thomas Gebhardt^2,*, Gayle M. Davey, William R. Heath and Francis R. Carbone^3,*

^* Department of Microbiology and Immunology, University of Melbourne and Walter and Eliza Hall Institute of Medical Research, Parkville, Australia

Naive and memory T cells show differences in their response to antigenic stimulation. We examined whether this difference extended to the peripheral deletion of T cells reactive to self-Ag or, alternatively, the induction of autoimmunity. Our results show that although both populations where susceptible to deletion, memory T cells, but not naive T cells, also gave rise to autoimmunity after in vivo presentation of skin-derived self-Ags. The same migratory dendritic cells presented self-Ag to both naive and memory T cell populations, but only the latter had significant levels of the effector molecule granzyme B. Memory T cells also expressed increased levels of the high affinity IL-2 receptor chain after self-Ag recognition. Provision of IL-2 signaling using a stimulatory complex of anti-IL-2 Ab and IL-2 drove the otherwise tolerant naive T cells toward an autoimmune response. Therefore, enhanced IL-2 signaling can act as a major selector between tolerance and autoimmunity.

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 the Australian National Heath and Medical Research Council, the Deutsche Forschungsgemeinschaft (GE 1666/1-1 to T.G.), and the Howard Hughes Medical Institute.

² J.W. and T.G. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Francis R. Carbone, Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia. E-mail address: fcarbone{at}unimelb.edu.au

⁴ Abbreviations used in this paper: B6, C57BL/6J; DC, dendritic cell; LN, lymph node.