CD8 T cell expansion and memory differentiation are facilitated by simultaneous and sustained exposure to antigenic and inflammatory milieu

The Journal of Immunology : Official Journal of the American Association of Immunologists
Angela Shaulov, Kaja Murali-Krishna

Abstract

Understanding the factors contributing to the generation of immune memory is important for rational vaccine design. In this study, we addressed the individual and combined roles of Ag and inflammation in sustaining the ability of primed CD8 T cells to clonally expand and differentiate into memory cells. We transferred CD8 T cells that were primed for a brief period into naive mice, mice infected with a pathogen not carrying the specific Ag (inflammation only), mice infected with a pathogen carrying the donor cell-specific Ag (inflammation plus Ag), or into mice exposed to soluble Ag (Ag only). We found that the donor CD8 T cells continued to proliferate in all the four conditions, but their ability to clonally expand and differentiate into memory cells was approximately 1000-fold higher when transferred into mice acutely infected with pathogen carrying the relevant Ag. Memory cells generated under conditions of sustained exposure to inflammation and Ag during the priming phase were superior in their ability to elicit recall responses on a per cell basis. Thus, simultaneous and sustained exposure of donor CD8 T cells to inflammatory and antigenic stimuli, following the initial priming phase, leads to the greatest expansion of CD...Continue Reading

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Citations

Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·Dietmar ZehnEd Palmer
Dec 17, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chelsi E WhiteNathan W Schmidt
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Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christopher M JewellDarrell J Irvine
Mar 2, 2016·The Journal of Clinical Investigation·Tyson J MoyerDarrell J Irvine
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Aug 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Byron B Au-YeungArthur Weiss

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