An interleukin-21- interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8 + T cells

Weiguo Cui, Ying Liu, Jason S. Weinstein, Joseph Craft, Susan M. Kaech

Research output: Contribution to journalArticlepeer-review

237 Scopus citations

Abstract

Memory CD8 + T cells are critical for long-term immunity, but the genetic pathways governing their formation remain poorly defined. This study shows that the IL-10-IL-21-STAT3 pathway is critical for memory CD8 + T cell development after acute LCMV infection. In the absence of either interleukin-10 (IL-10) and IL-21 or STAT3, virus-specific CD8 + T cells retain terminal effector (TE) differentiation states and fail to mature into protective memory T cells that contain self-renewing central memory T cells. Expression of Eomes, BCL-6, Blimp-1, and SOCS3 was considerably reduced in STAT3-deficient memory CD8 + T cells, and BCL-6- or SOCS3-deficient CD8 + T cells also had perturbed memory cell development. Reduced SOCS3 expression rendered STAT3-deficient CD8 + T cells hyperresponsive to IL-12, suggesting that the STAT3-SOCS3 pathway helps to insulate memory precursor cells from inflammatory cytokines that drive TE differentiation. Thus, memory CD8 + T cell precursor maturation is an active process dependent on IL-10-IL-21-STAT3 signaling.

Original languageEnglish (US)
Pages (from-to)792-805
Number of pages14
JournalImmunity
Volume35
Issue number5
DOIs
StatePublished - Nov 23 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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