%A Pham,Nhat-Long %A Badovinac,Vladimir %A Harty,John %D 2011 %J Frontiers in Immunology %C %F %G English %K CD8 T cells,effector/memory differentiation,inflammatory cytokines,signal 3 %Q %R 10.3389/fimmu.2011.00004 %W %L %M %P %7 %8 2011-February-11 %9 Original Research %+ Prof John Harty,University of Iowa,Microbiology,Iowa City,IA,United States,john-harty@uiowa.edu %+ Prof John Harty,University of Iowa,Graduate Program in Immunology,Iowa City,IA,United States,john-harty@uiowa.edu %# %! Inflammatory cytokines regulate CD8 T Cell Differentiation %* %< %T Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo %U https://www.frontiersin.org/articles/10.3389/fimmu.2011.00004 %V 2 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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 secondary antigen-specific memory CD8 T cells.