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Nat Rev Immunol. 2016 Feb;16(2):102-11. doi: 10.1038/nri.2015.10. Epub 2016 Jan 19.

The multifaceted role of CD4(+) T cells in CD8(+) T cell memory.

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Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California 94143, USA.
Department of Internal Medicine (Rheumatology), Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 2081, USA.


Following infection, T cells differentiate into a heterogeneous population of effector T cells that can mediate pathogen clearance. A subset of these effector T cells possesses the ability to survive long term and mature into memory T cells that can provide long-term immunity. Understanding the signals that regulate the development of memory T cells is crucial to efforts to design vaccines capable of eliciting T cell-based immunity. CD4(+) T cells are essential in the formation of protective memory CD8(+) T cells following infection or immunization. However, until recently, the mechanisms by which CD4(+) T cells act to support memory CD8(+) T cell development following infection were unclear. Here, we discuss recent studies that provide insight into the multifaceted role of CD4(+) T cells in the regulation of memory CD8(+) T cell differentiation.

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