IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells.
Regulatory T cells (T(Reg)) control immune responses to self and nonself Ags. The relationship between Ag-driven IL-10-secreting T(Reg) (IL-10-T(Reg)) and naturally occurring CD4(+)CD25(+) T(Reg) is as yet unclear. We show that mouse IL-10-T(Reg) obtained using either in vitro or in vivo regimens of antigenic stimulation did not express the CD4(+)CD25(+) T(Reg)-associated transcription factor Foxp3. However, despite the absence of Foxp3 expression, homogeneous populations of IL-10-T(Reg) inhibited the in vitro proliferation of CD4(+)CD25(-) T cells with a similar efficiency to that of CD4(+)CD25(+) T(Reg). This inhibition of T cell proliferation by IL-10-T(Reg) was achieved through an IL-10-independent mechanism as seen for CD4(+)CD25(+) T(Reg) and was overcome by exogenous IL-2. Both IL-10-T(Reg) and CD4(+)CD25(+) T(Reg) were similar in that they produced little to no IL-2. These data show that Foxp3 expression is not a prerequisite for IL-10-T(Reg) activity in vitro or in vivo, and suggest that IL-10-T(Reg) and naturally occurring CD4(+)CD25(+) T(Reg) may have distinct origins.
Vieira
Pedro L
PL
Division of Immunoregulation, The National Institute for Medical Research, London, United Kingdom. pvieira@nimr.mrc.ac.uk
Christensen
Jillian R
JR
Minaee
Sophie
S
O'Neill
Emma J
EJ
Barrat
Franck J
FJ
Boonstra
André
A
Barthlott
Thomas
T
Stockinger
Brigitta
B
Wraith
David C
DC
O'Garra
Anne
A
D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; C074815:myelin basic protein 1-9; D016753:Interleukin-10