Differential role of "Signal 3" inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo.

Frontiers in Immunology
Nhat-Long L PhamJohn T Harty

Abstract

Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and seconda...Continue Reading

Citations

Dec 25, 2013·The Journal of Experimental Medicine·Gabriel R Starbeck-MillerJohn T Harty
Mar 21, 2015·Nature Reviews. Immunology·Josh CrouseAnnette Oxenius
Dec 30, 2014·Frontiers in Immunology·Hope O'Donnell, Stephen J McSorley
Nov 23, 2016·European Journal of Immunology·Mélissa MathieuNathalie Labrecque
Jul 22, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie T KimJohn T Harty
Apr 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael M OpataRobin Stephens
Nov 29, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gabriel R Starbeck-MillerJohn T Harty
Oct 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua J ObarLeo Lefrançois

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transgenic
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