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.
Collison
Lauren W
LW
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Chaturvedi
Vandana
V
Henderson
Abigail L
AL
Giacomin
Paul R
PR
Guy
Cliff
C
Bankoti
Jaishree
J
Finkelstein
David
D
Forbes
Karen
K
Workman
Creg J
CJ
Brown
Scott A
SA
Rehg
Jerold E
JE
Jones
Michael L
ML
Ni
Hsiao-Tzu
HT
Artis
David
D
Turk
Mary Jo
MJ
Vignali
Dario A A
DA
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