Targeting antigen to diverse APCs inactivates memory CD8+ T cells without eliciting tissue-destructive effector function

Kenna, Tony J., Waldie, Tanya, McNally, Alice, Thomson, Meagan, Yagita, Hideo, Thomas, Ranjeny, & Steptoe, Raymond J. (2010) Targeting antigen to diverse APCs inactivates memory CD8+ T cells without eliciting tissue-destructive effector function. Journal of Immunology, 184(2), pp. 598-606.

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Abstract

Memory T cells develop early during the preclinical stages of autoimmune diseases and have traditionally been considered resistant to tolerance induction. As such, they may represent a potent barrier to the successful immunotherapy of established autoimmune diseases. It was recently shown that memory CD8+ T cell responses are terminated when Ag is genetically targeted to steady-state dendritic cells. However, under these conditions, inactivation of memory CD8+ T cells is slow, allowing transiently expanded memory CD8+ T cells to exert tissue-destructive effector function. In this study, we compared different Ag-targeting strategies and show, using an MHC class II promoter to drive Ag expression in a diverse range of APCs, that CD8+ memory T cells can be rapidly inactivated by MHC class II+ hematopoietic APCs through a mechanism that involves a rapid and sustained downregulation of TCR, in which the effector response of CD8+ memory cells is rapidly truncated and Ag-expressing target tissue destruction is prevented. Our data provide the first demonstration that genetically targeting Ag to a broad range of MHC class II+ APC types is a highly efficient way to terminate memory CD8+ T cell responses to prevent tissue-destructive effector function and potentially established autoimmune diseases. Copyright © 2010 by The American Association of Immunologists, Inc.

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ID Code: 94066
Item Type: Journal Article
Refereed: Yes
Keywords: major histocompatibility antigen class 2, T lymphocyte antigen, antigen, HLA antigen class 2, adoptive transfer, antigen expression, antigen presenting cell, article, CD8+ T lymphocyte, cell activation, cell density, cell expansion, comparative study, controlled study, effector cell, gene inactivation, gene targeting, hematopoietic cell, mouse, nonhuman, priority journal, signal transduction, tissue injury, animal, antigen presentation, autoimmune disease, genetics, immunological memory, immunology, promoter region, Animals, Antigen-Presenting Cells, Antigens, Autoimmune Diseases, CD8-Positive T-Lymphocytes, Histocompatibility Antigens Class II, Immunologic Memory, Mice, Promoter Regions, Genetic
DOI: 10.4049/jimmunol.0900032
ISSN: 0022-1767
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 The American Association of Immunologists, Inc.
Deposited On: 22 Mar 2016 22:54
Last Modified: 24 Mar 2016 04:06

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