IL-12-programmed long-term CD8+ T cell responses require STAT4

Qingsheng Li, Cheryl Eppolito, Kunle Odunsi, Protul A. Shrikant

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Immunological adjuvants activate innate immune cells for Ag presentation and elicitation of cytokines like IL-12 that promote T cell expansion and effector differentiation. An important but elusive aim for most immunization strategies is to produce memory T cells that provide durable immunity. Recent evidence demonstrates that the contest of Ag presentation instructionally programs T cells for short- and long-term responses. However, the role and mechanisms by which cytokines like IL-12 condition CD8 T cells for long-term responses remain relatively uncharacterized. In this study, we show that brief exposure (20 h) of naive TCR-transgenic CD8 cells to IL-12 during Ag stimulation leads to transient phosphorylation of STAT4 for robust effector differentiation. Moreover, the IL-12-induced STAT4 engenders greater clonal expansion of the Ag-activated CD8 cells by regulating the expression of the transcriptional factor Bcl3- and Bcl2-related genes that promote survival of Ag-activated CD8 cells. Remarkably, the IL-12-conditioned CD8 T cells demonstrate increased sensitivity to IL-7 and IL-15, whereby they are rendered "fit" for homeostatic self-renewal as well as augmented CD4-dependent recall responses that are effective at controlling Salmonella infection in vivo. This information provides new insights into mechanisms by which IL-12 conditions CD8 T cells for long-term immunity, which is likely to benefit development of new strategies for the use of IL-12 in infectious diseases and cancer.

Original languageEnglish (US)
Pages (from-to)7618-7625
Number of pages8
JournalJournal of Immunology
Volume177
Issue number11
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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