T cell-intrinsic role of IL-6 signaling in primary and memory responses.
Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1β to block the suppressive effect of Tregs on CD4(+) T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Rα-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4(+) T cell memory formation.DOI: http://dx.doi.org/10.7554/eLife.01949.001.
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Simone A
SA
Nish
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Dominik
D
Schenten
Max Planck Institute for Neurological Research, Cologne, Germany.
F Thomas
FT
Wunderlich
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Scott D
SD
Pope
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Yan
Y
Gao
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Namiko
N
Hoshi
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Shuang
S
Yu
Department of Biostatistics, Yale School of Public Health, New Haven, United States.
Xiting
X
Yan
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Heung Kyu
HK
Lee
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Lesley
L
Pasman
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Igor
I
Brodsky
Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
Brian
B
Yordy
Department of Biostatistics, Yale School of Public Health, New Haven, United States.
Hongyu
H
Zhao
Max Planck Institute for Neurological Research, Cologne, Germany.
Jens
J
Brüning
Department of Immunobiology, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States ruslan.medzhitov@yale.edu.
Ruslan
R
Medzhitov
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D007156:Immunologic Memory / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053698:Interleukin-6 Receptor alpha Subunit / Q000172:deficiency / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D053698:Interleukin-6 Receptor alpha Subunit; D011994:Recombinant Proteins; D010047:Ovalbumin
T cells; cytokines; memory; regulatory T cells