Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation

David, A., Crawford, F., Garside, P. , Kappler, J. W., Marrack, P. and Macleod, M. (2014) Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation. Proceedings of the National Academy of Sciences of the United States of America, 111(21), pp. 7735-7740. (doi:10.1073/pnas.1406218111) (PMID:24821788) (PMCID:PMC4040609)

David, A., Crawford, F., Garside, P. , Kappler, J. W., Marrack, P. and Macleod, M. (2014) Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation. Proceedings of the National Academy of Sciences of the United States of America, 111(21), pp. 7735-7740. (doi:10.1073/pnas.1406218111) (PMID:24821788) (PMCID:PMC4040609)

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Abstract

Autoimmune diseases are driven by immune cells that recognize self-tissues. A major goal for treatment strategies for autoimmune diseases is to turn off or tolerize self-reactive immune cells such as CD4 T cells that coordinate tissue damage in many autoimmune diseases. Autoimmune diseases are often diagnosed many years following their onset. The self-reactive CD4 T cells that must be tolerized, therefore, are previously activated or memory CD4 T cells. Little is known about whether tolerance can be induced in memory CD4 T cells. This paper demonstrates that memory CD4 T cells survive initial exposure to tolerance-inducing signals but that a second activation signal leads to cell death. This study has important implications for immunotherapeutic strategies for autoimmune diseases.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and Macleod, Dr Megan
Authors: David, A., Crawford, F., Garside, P., Kappler, J. W., Marrack, P., and Macleod, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Copyright Holders:Copyright © 2014 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 111(21):7735-7740
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
581051Molecular requirements for the induction of tolerance in activated and memory CD4 T cells.Paul GarsideArthritis Research UK (ARUK)19905RI INFECTION IMMUNITY & INFLAMMATION