title: An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells.
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.
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Weiguo
authors: W
authors: Cui
authors: Ying
authors: Y
authors: Liu
authors: Jason S
authors: JS
authors: Weinstein
authors: Joseph
authors: J
authors: Craft
authors: Susan M
authors: SM
authors: Kaech
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D007156:Immunologic Memory / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: C491198:Eomes protein, mouse; D007378:Interleukins; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D016753:Interleukin-10; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000098546:Interleukin-21