IL-35-mediated induction of a potent regulatory T cell population.
Regulatory T cells (T(reg) cells) have a critical role in the maintenance of immunological self-tolerance. Here we show that treatment of naive human or mouse T cells with IL-35 induced a regulatory population, which we call 'iT(R)35 cells', that mediated suppression via IL-35 but not via the inhibitory cytokines IL-10 or transforming growth factor-β (TGF-β). We found that iT(R)35 cells did not express or require the transcription factor Foxp3, and were strongly suppressive and stable in vivo. T(reg) cells induced the generation of iT(R)35 cells in an IL-35- and IL-10-dependent manner in vitro and induced their generation in vivo under inflammatory conditions in intestines infected with Trichuris muris and within the tumor microenvironment (B16 melanoma and MC38 colorectal adenocarcinoma), where they contributed to the regulatory milieu. Thus, iT(R)35 cells constitute a key mediator of infectious tolerance and contribute to T(reg) cell-mediated tumor progression. Furthermore, iT(R)35 cells generated ex vivo might have therapeutic utility.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Lauren W
LW
Collison
Vandana
V
Chaturvedi
Abigail L
AL
Henderson
Paul R
PR
Giacomin
Cliff
C
Guy
Jaishree
J
Bankoti
David
D
Finkelstein
Karen
K
Forbes
Creg J
CJ
Workman
Scott A
SA
Brown
Jerold E
JE
Rehg
Michael L
ML
Jones
Hsiao-Tzu
HT
Ni
David
D
Artis
Mary Jo
MJ
Turk
Dario A A
DA
Vignali
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D007378:Interleukins; C532417:interleukin-35, human