IL-23 promotes the production of IL-17 by antigen-specific CD8 T cells in the absence of IL-12 and type-I interferons.
In contrast to CD4 T cells, CD8 T cells inherently differentiate into IFN-gamma-producing effectors. Accordingly, while generation of IFN-gamma-producing Th1 CD4 T cells was profoundly impaired in mice deficient for both type-I IFN and IL-12 signaling in response to infection with Listeria monocytogenes, generation of Ag-specific, IFN-gamma-producing CD8 T cells was unimpaired. However, a fraction of these CD8 T cells also produced IL-17 in an IL-23-dependent manner. Furthermore, the addition of IL-23 in vitro was sufficient for some naive CD8 T cells to differentiate into IFN-gamma/IL-17 dual-producing cells and was associated with increased expression of ROR-gammat and ROR-alpha. Addition of IL-6 and TGF-beta to IL-23 further augmented ROR-gammat and ROR-alpha expression and suppressed Eomes expression, thereby enhancing IL-17 production by CD8 T cells. A loss of cytotoxic function accompanied the production of IL-17, as the addition of IL-6 and TGF-beta resulted in a marked reduction of granzyme B and perforin expression. Thus, CD8 T cells retain sufficient plasticity to respond to environmental cues and can acquire additional effector functions in response to their environmental context.
Curtis
Meredith M
MM
Department of Immunology, University of Washington School of Medicine, Seattle, 98195, USA.
Way
Sing Sing
SS
Wilson
Christopher B
CB
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007370:Interferon Type I / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000098815:T-bet Transcription Factor
C491198:Eomes protein, mouse; D018984:Epitopes, T-Lymphocyte; D007370:Interferon Type I; D020381:Interleukin-17; D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma