AUTHOR=Pham Nhat-Long , Badovinac Vladimir , Harty John TITLE=Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo JOURNAL=Frontiers in Immunology VOLUME=2 YEAR=2011 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2011.00004 DOI=10.3389/fimmu.2011.00004 ISSN=1664-3224 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 secondary antigen-specific memory CD8 T cells.