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

Immunity. 2011 Nov 23;35(5):792-805. doi: 10.1016/j.immuni.2011.09.017.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Immunologic Memory / immunology*
  • Interleukin-10 / metabolism*
  • Interleukins / metabolism*
  • Mice
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Eomes protein, mouse
  • Interleukins
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-6
  • STAT3 Transcription Factor
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • T-Box Domain Proteins
  • Transcription Factors
  • Interleukin-10
  • Positive Regulatory Domain I-Binding Factor 1
  • interleukin-21