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

Nhat Long L Pham, Vladimir P. Badovinac, John T. Harty

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberArticle 4
JournalFrontiers in Immunology
Volume2
Issue numberFEB
DOIs
StatePublished - Dec 1 2011

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Cell Differentiation
Cytokines
T-Lymphocytes
Interleukin-12
Interferon Type I
Dendritic Cells
CD8 Antigens
Infection
Immunization
Phenotype
Antigens
Peptides

Keywords

  • Inflammatory cytokines
  • Memory CD8 T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Differential role of "signal 3" inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. / Pham, Nhat Long L; Badovinac, Vladimir P.; Harty, John T.

In: Frontiers in Immunology, Vol. 2, No. FEB, Article 4, 01.12.2011.

Research output: Contribution to journalArticle

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