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Effects of Signal 3 during CD8 T cell priming: Bystander production of IL-12 enhances effector T cell expansion but promotes terminal differentiation. Vaccine 2009 Mar 26;27(15):2177-87

Date

02/10/2009

Pubmed ID

19201385

Pubmed Central ID

PMC2803112

DOI

10.1016/j.vaccine.2009.01.088

Scopus ID

2-s2.0-61549120751   79 Citations

Abstract

Adjuvants are commonly used in vaccines to augment immune response, but how the inflammatory cytokines elicited by adjuvants directly influence effector and memory CD8 T cell differentiation remains poorly characterized. Here, we used a peptide-pulsed dendritic cell (DC) vaccination model to examine the role of primary cytokines, IL-12 and IFNgamma, elicited by CpG-B adjuvant on CD8 T cell priming and memory CD8 T cell development. During DC vaccination, simultaneous exposure to antigen and a heterologous Listeria infection, CpG-B or IL-12 enhanced a portion of the effector CD8 T cells to expand and differentiate to a larger extent. Simultaneously, this also decreased their ability to become long-lived memory CD8 T cells. However, development of memory CD8 T cells and their precursors was largely unaffected by the additional inflammatory cytokines. Moreover, IL-12 production by the antigen-presenting cell (APC) was not required during DC+CpG vaccination or Listeria infection, but rather 'bystander' macrophages and DCs appeared to be the physiologically relevant cellular sources of this cytokine. Furthermore, IFNgamma induced by CpG was required in vivo for optimal production of IL-12, which in turn, influenced effector CD8 T cell longevity. Together, these findings demonstrate the importance of an interconnected multicellular network between APCs, naïve T cells and bystander cells of the innate immune system that regulate effector and memory CD8 T cell development during vaccination.

Author List

Cui W, Joshi NS, Jiang A, Kaech SM

Author

Weiguo Cui PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adjuvants, Immunologic
Animals
CD8-Positive T-Lymphocytes
Cell Differentiation
Cells, Cultured
DNA
Dendritic Cells
Immunologic Memory
Interferon-gamma
Interleukin-12
Listeriosis
Lymphocyte Activation
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Oligodeoxyribonucleotides
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc