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CD8 T cell responses to murine gamma-herpesvirus 68: viral persistence shapes the immune response.

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Call No.	QR185.8.T2 O23 2006
Author	Obar, Joshua J.
Title	CD8 T cell responses to murine gamma-herpesvirus 68: viral persistence shapes the immune response.
Date	2006
Abstract	Vaccines are one the greatest advances in public health. Vaccines work by priming cells of the adaptive immune system in such a way that they remember that they have encountered a specific antigen before. This then allows those cells to respond faster and more potently to any future encounter with that antigen. An understanding of the process by which na√Øve CD8 T cells develop into effector cytotoxic T lymphocytes (CTL) and eventually into memory cells has been developing in recent years. However, most of this knowledge has been accumulated using models of acute pathogens. An understanding of how the development of CTL and memory cells is affected by pathogen persistence will be critical in the development of the next generation of vaccines to treat or prevent chronic infections, such as HIV or hepatitis C. In this thesis, we have used a model γ-herpesvirus, murine gammaherpesvirus 68 (γHV-68), to begin to understand how latent viruses may affect the developing CD8 T cell response. We have found that memory cells induced by this latent virus differed from those induced by acute pathogens. Memory cells induced by this latent virus did not develop into antigen-independent memory cells and required antigen in order to maintain their proliferative renewal. These cells also failed to completely up-regulate Bcl-2 expression or gain the ability to produce IL-2, which are both seen during memory cell differentiation following acute pathogen encounter. In addition, memory cells specific for antigens presented largely during the acute viral replication stage differed from those specific for antigens from the latent stage of the infection in terms of phenotype, responsiveness to homeostatic cytokines and cytotoxic ability. Lastly, memory cells from this latent infection were surprisingly more potent at mediating protective immunity against future viral infection. These data begin to shed light on the effects that long-term persistence of antigen can have on the developing CD8 T cell response.
Description	xiii, 212 leaves : ill. 28 cm.
Format	application/pdf
Advisor	Edward J. Usherwood.
Subject	T cells. Immunologic memory. Latent virus diseases -- Immunological aspects. Herpesvirus diseases. Cell-mediated cytotoxicity. CD8-Positive T-Lymphocytes -- immunology. T-Lymphocytes
College	Dartmouth Medical School -- Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.109

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	CD8 T CELL RESPONSES TO MURINE GAMMA-HERPESVIRUS 68: VIRAL PERSISTENCE SHAPES THE IMMUNE RESPONSE A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Microbiology & Immunology By Joshua J. Obar DARTMOUTH COLLEGE Hanover, New Hampshire April 27, 2006 Examining Committee: _____________________________ (Chair) Edward J. Usherwood, Ph.D. _____________________________ William R. Green, Ph.D. _____________________________ Randolph J. Noelle, Ph.D. _____________________________ Raymond M. Welsh, Ph.D. ____________________________ Charles K. Barlowe, Ph.D. Dean of Graduate Studies

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