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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