During the plague of Athens in 430 b.c., the Greek historian
Thucydides made the first known reference to immunological memory when he observed
that the “same man was never attacked twice.” More than two thousand years later,
technological advances have allowed scientists to begin unraveling the
molecular underpinnings of the phenomenon. It is now appreciated that the main
components of the adaptive immune system–B cells, CD4 T cells and CD8 T cells–respond to infections by developing specialized abilities that can often
mediate protection against re-infection or–in the case of pathogens that are
controlled rather than eliminated from the body–disease. The long-lived B
cells, CD4 T cells and CD8 T cells that perform these vital functions are known
as “memory” cells.
The laboratory of Rafi Ahmed at Emory University has long
been at the forefront of research into immunological memory, particularly as it
pertains to CD8 T cells. In a new free-access paper in the journal International
Immunology, Ahmed and colleagues review how changes in gene expression
contribute to the enhanced infection-fighting functions of memory CD8 T cells,
and outline how these functions are inherited by the progeny of memory cells
via the wonders of epigenetics. The
review concludes by suggesting that it may eventually become possible to correct
memory cell dysfunction by targeting gene regulation mechanisms.
International Immunology Advance Access published online on
August 23, 2010
International Immunology, doi:10.1093/intimm/dxq437
review-article
Making memories that last a lifetime: heritable functions of
self-renewing memory CD8 T cells
Ben Youngblood1,2, Carl W. Davis1,2 and Rafi Ahmed1,2
1 Emory Vaccine Center, Atlanta, GA 30329, USA
2 Department of Microbiology and Immunology, Emory University
School of Medicine, Atlanta, GA 30322, USA
Clonal expansion of virus-specific naive T cells during an
acute viral infection results in the formation of memory CD8 T cells that
provide the host with long-term protective immunity against the pathogen.
Memory CD8 T cells display enhanced effector functions compared with their
naive precursors, allowing them to respond more rapidly and effectively to
antigen re-encounter. The enhanced functions of memory CD8 T cells are mediated
by heritable changes in gene regulation. Expression of select transcription
factors along with locus-specific epigenetic modifications are coupled to and
are essential in the formation of memory-specific gene expression patterns.
Here, we will review the changes in gene expression that accompany development
of memory CD8 T cells and discuss chromatin modifications as a potential means
for heritable propagation of these changes during homeostatic cell division of
self-renewing memory CD8 T cells. Also, we will discuss therapies that
manipulate heritable gene regulation as a potential mechanism to restore
function to non-functional memory CD8 T cells to combat chronic viral
infection.
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