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
Date
11/29/2011Pubmed ID
22118527Pubmed Central ID
PMC3431922DOI
10.1016/j.immuni.2011.09.017Scopus ID
2-s2.0-82055208627 (requires institutional sign-in at Scopus site) 302 CitationsAbstract
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.
Author List
Cui W, Liu Y, Weinstein JS, Craft J, Kaech SMMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Cell Differentiation
Gene Expression Regulation, Developmental
Immunologic Memory
Interleukin-10
Interleukins
Mice
Mice, Knockout
Positive Regulatory Domain I-Binding Factor 1
Proto-Oncogene Proteins c-bcl-6
STAT3 Transcription Factor
Signal Transduction
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
T-Box Domain Proteins
Transcription Factors