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The role of CD154/CD40 interactions in the development and persistence of CD4+ T cell-mediated immunity.

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Call No.	QR186.6.C42 M54 2000
Author	Miga, Amy J.
Title	The role of CD154/CD40 interactions in the development and persistence of CD4+ T cell-mediated immunity.
Date	2000
Abstract	The data presented herein demonstrate the requirement for CD154/CD40 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Blockade of CD154/CD40 interactions causes a decrease in T cell and macrophage cellular infiltration within the CNS, and a significant decrease in IFN-γ production by responding neuroantigen-specific T cells. We also show that treatment of diseased animals with anti-CD154 prevents disease relapse in the relapsing/remitting model of EAE, and that antibody treatment affords protection in a chronic EAE model. We have also found that treating recipients of encephalitogenic T cells with anti-CD154 delays disease onset and decreases severity, and CD40-deficient animals are less susceptible to EAE induced by adoptive transfer. These results support a role for CD154/CD40 interactions in both the initiation and progression of EAE, and are further verified by studies using chimeric mice. Experiments with CD40 chimeric mice confirm the pivotal role for CD40 in disease development, and its supportive role in disease persistence. These studies further show that, in the absence of adjuvant, CD154/CD40 interactions are essential in promoting sustained antigen-specific T cell population expansion in vivo. The lack of T cell population expansion observed in the absence of a CD40 signal is not associated with a permanent state of T cell tolerance, but is associated with a decrease in the Th1-type cytokine, IFN-γ. Of important physiologic relevance, we demonstrate the potency of CD40 in causing long-term DC persistence and antigen retention. Collectively, the data suggest a pivotal role for CD40 on DCs in the generation of robust, sustained T cell-mediated immune responses. Such findings demonstrate that the involvement of CD40 in antigen retention is likely a major determining factor in T cell expansion.
Description	1 online resource (xi, 172 leaves) : illustrations
Format	application/pdf
Advisor	Noelle, Randolph J.
Subject	CD antigens. ; T cells -- Receptors. ; Tumors -- Immunological aspects. ; Mice -- Immunology. ; CD4-Positive T-Lymphocytes. ; Antigens CD40.
College	Dartmouth Medical School -- Department of Biochemistry.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D)--Dartmouth College.
Copyright	In Copyright. This material is protected by copyright and/or related rights. You are free to use this material in any way that is permitted by copyright law that applies to your use. For other uses, you need to obtain permission from the rights-holder(s). http://rightsstatements.org/page/InC/1.0/
DOI	https://doi.org/10.1349/ddlp.2828

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The role of CD154/CD40 interactions in the development and persistence of CD4+ T cell-mediated immunity.

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