Memory T Cells

223 Pages·2010·2.891 MB·English

by  Toshinori Nakayama, Motoko Y. Kimura (auth.), Maurizio Zanetti MD, Stephen P. Schoenberger PhD (eds.)

Memory T Cells
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research
JOHN D. LAMBRIS, University of Pennsylvania
RODOLFO PAOLETTI, University of Milan
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MEMORY T CELLS
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Memory T Cells
Edited by
Maurizio Zanetti, MD
The Laboratory of Immunology, Department of Medicine and Moores Cancer
Center, University of California, San Diego, La Jolla, California, USA
Stephen P. Schoenberger, PhD
Laboratory of Cellular Immunology, La Jolla Institute for Allergy
and Immunology, La Jolla, California, USA
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Landes Bioscience
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Library of Congress Cataloging-in-Publication Data
Memory T cells / edited by Maurizio Zanetti and Stephen P. Schoenberger.
p. ; cm. -- (Advances in experimental medicine and biology ; v. 684)
Includes bibliographical references and index.
ISBN 978-1-4419-6450-2
1. Immunologic memory. 2. T cells. I. Zanetti, M. (Maurizio) II. Schoenberger, Stephen P. III. Series:
Advances in experimental medicine and biology ; v. 684.
[DNLM: 1. T-Lymphocytes--immunology. 2. Autoimmunity. 3. Immunity, Cellular. 4. Immunologic
Memory. W1 AD559 v.684 2010 / QW 568 M5336 2010]
QR185.35.M46 2010
616.07’9--dc22
2010014175
DEDICATION
In memory of Nerita Zanetti (October 5, 2009).
v
PREFACE
Immunological memory has fascinated microbiologists and immunologists for
decades as one of the new frontiers to conquer to better understand the response to
pathogens, cancer and vaccination. Over the past decade, attention has turned to the
intrinsic properties of the memory T cells themselves, as it has become clear that
the eradication of both infected cells and tumors requires T cells. This book is an
attempt to capture the wave of discoveries associated with these recent studies. Its
chapters represent a wide collection of topics related to memory T cells by labora-
tories that have invested their skills and knowledge to understand the biology and
the principles upon which memory T cells are generated, maintained and expanded
upon re-encounter with antigen. Ultimately, these studies are all aimed at a better
understanding of the function of memory T cells in protection against disease.
Little is still known about the transcriptional events regulating the emergence of
memory T cells. Chapter 1 discusses the role of Schnurri-2, which plays a critical role
in cell growth, signal transduction and lymphocyte development, in the generation
of memory CD4 T cells. Nakayama and Kimura point out that Schnurri-2 mediates
repression of NF-(cid:2)B hence enabling cell survival during the critical time of memory
cell generation. In Chapter 2, Rocha and colleagues focus on how transcriptional
regulation in memory CD8 T-cell responses allows them to more efficiently respond
to antigen stimulation by modifying their cell cycle machinery in order to divide
faster, improving DNA repair and enacting other cell survival mechanisms.
The role of cytokines, novel costimulatory molecules and other signals coming
from the microenvironment in the generation and maintenance of memory T cells is
discussed in Chapters 3-5. In Chapter 3, Sprent and colleagues discuss the importance
of IL-2 signaling during the contraction phase in memory CD8 T-cell differentiation.
At the time where most antigen-specific CD8 T cells disappear by apoptosis, IL-2 sig-
nals rescue CD8 T cells from cell death and provide a durable increase in cell counts.
This work shows that IL-2 signals during different phases of an immune response
are key in optimizing CD8 T-cell functions, affecting both primary and secondary
responses. Chapter 4 sees Butler and Harty discussing the role of inflammation in
the generation and maintenance of memory T cells showing that these two phases
are influenced by a multitude of factors, including inflammatory cytokines that can
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viii Preface
act on T cells during their differentiation, actually shaping the quantity and quality
of memory T cells, and the rate at which functional memory populations develop.
Chapter 5 points to a critical role of OX40 (CD134) in T-cell memory generation.
Weinberg argues that enhancing OX40 signaling during antigen priming using OX40
agonists increases memory T-cell development. He also discusses the therapeutic
potential of OX40 agonists and antagonists in human clinical trials.
Chapters 6-9 discuss the generation and maintenance of memory CD8 T cells
during acute or chronic viral infection, in the context of the efficiency of recall re-
sponses and protection. In Chapter 6, Marzo, Sowell, and Scott seek to establish a
correlation between precursor frequency and the differentiation of memory T cells
following acute viral infection. In Chapter 7, Ahmed and colleagues discuss the
parameters that influence memory CD8 T-cell generation and maintenance in the
context of acute vs. chronic viral infection. They also discuss new surprising findings
linking mTOR function with the generation of memory T cells. In the same vein
Walker and Sifka in Chapter 8 examine the longevity of memory CD8 T cells after
acute viral infection by a variety of methods. Their goal is to identify the optimal
combination of functional characteristics required for protective immunity against
the infectious disease. In Chapter 9, Zanetti and colleagues review the available
information to formulate a set of principles to guide the generation of more effec-
tive vaccines that elicit protective memory T cells. The working principles for the
generation of protective memory T cells by vaccination are discussed both in the
context of the immunologically-inexperienced and immunologically-experienced
individual.
In Chapter 10, Vaccari and Franchini present and discuss data on the induction of
memory T-cell responses in non-human primates, and argue that these experimental
models yield information that more closely matches the events that take place in
humans with respect to induction and maintenance of memory T cells. Colpitts and
Scott in Chapter 11 examine a few experimental models used to elucidate the nature
of the memory T cells that are generated during parasitic infections, and suggest that
long-term immunity induced by vaccination is a realistic goal to control parasitic
infections.
Chapters 12-15 review what is currently known about the role of memory T cells
in cancer and provide hints about monitoring memory T-cells responses after vac-
cination. In Chapter 12, Alderson and Murphy discuss how memory T-cell responses
generated by vaccination are impacted upon by concomitant immune stimulation
by adjuvants of novel formulation or cytokines. The authors also discuss whether
initial tumor regression and generation of sustained anti-tumor immunity have dif-
ferent immunological signaling requirements. Chapter 13 summarizes a survey in
colorectal cancer patients correlating the presence of memory T cells infiltrating
tumors in humans and clinical outcome. Camus and Galon provide evidence that a
strong and coordinated in situ T-cell response, with accumulation of memory T cells
within primary tumors, dramatically reduces the risks of relapse. This highly significant
correlation between the quality of the in situ immune response, tumor dissemination,
and clinical outcome suggests that attempts to vaccinate cancer patients may ultimately
Preface ix
succeed if the effect documented in the natural evolution of colorectal cancer can be
generalized to other forms of cancer. Chapter 14 presents a state-of-the-art review by
Marincola and colleagues of current methods to monitor T-cell immune responses
to vaccination in cancer patients. Ex vivo assays to evaluate tumor-specific T-cell
responses at the immunological and transcriptional level have demonstrated tumor
recognition and T-cell activation, implying that tumor-specific T-cell induction indeed
occurs in vivo. However, at the present time these assays alone are not adequate to
predict tumor regression.
Finally, in Chapter 15, Henson and Akbar discuss a crucial issue in the biology
of memory T cells: memory T-cell homeostasis and senescence during aging. The
authors argue that because life expectancy has dramatically increased and continues
to increase, memory T cells will also have to span over longer times. Our current
understanding is that T-cell memory wanes during aging as evidenced by the suscep-
tibility of old individuals to infection by organisms to which they were previously
immune. They show that this loss of memory T cells originates from antigen-driven
differentiation and exhaustion, and telomere erosion.
The field of study of memory T cells is relatively young and the unknowns are
still numerous, but the intellectual and medical rewards promised by a better under-
standing of the biology of memory T-cell generation, differentiation and maintenance,
are formidable not only to understand the immunodynamics of natural adaptive T-cell
responses but also for the induction of protective T-cell responses by vaccination.
The compendium of topics assembled in this book and the ideas discussed
in it represent our initial effort to lay the foundation for a comprehensive view of
the field and its future potential. The scientific facts and premises presented here
constitute, in our view, the seeds from which new work will originate hopefully
increasing our knowledge and ultimately having an impact on our fight against
many human diseases.
We thank Ronald G. Landes for having encouraged us to undertake this
project.
Maurizio Zanetti, MD
The Laboratory of Immunology, Department of Medicine and Moores Cancer
Center, University of California, San Diego, La Jolla, California, USA
Stephen P. Schoenberger, PhD
Laboratory of Cellular Immunology, La Jolla Institute for Allergy
and Immunology, La Jolla, California, USA
ABOUT THE EDITORS...
MAURIZIO ZANETTI, MD, is a Professor of Medicine at the University of
California, San Diego (UCSD), and a member of the Moores UCSD Cancer Center.
He is the Director of the Immunology laboratory at the Moores UCSD Cancer Center
as well as of the Graduate Course in Immunology at UCSD. His main interests
include the generation and maintenance of memory T cells with protective value
against disease. These responses are studied with respect to cancer and influenza
virus infection. His work in humans is devoted to to the immunology of telomerase
reverse transcriptase, a prototype universal cancer antigen. He served in the program
Committee of the American Society of Immunology, and as an Associate Editor for the
Journal of Immunology and Cellular Immunology. He is a member of the American
Association of Immunologists and American Society for Clinical Investigation. Dr.
Zanetti received his MD from the University of Padova, Italy.
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