Role for IL-10 in suppression mediated by peptide-induced regulatory T cells in vivo.
Regulatory CD4(+) T cells were induced in the Tg4 TCR transgenic mouse specific for the N-terminal peptide (Ac1-9) of myelin basic protein by intranasal administration of a high-affinity MHC-binding analog (Ac1-9[4Y]). Peptide-induced tolerant cells (PItol) were anergic, failed to produce IL-2, but responded to Ag by secretion of IL-10. PItol cells were predominantly CD25(-) and CTLA-4(+) and their anergic state was reversed by addition of IL-2 in vitro. PItol cells suppressed the response of naive Tg4 cells both in vitro and in vivo. The in vitro suppression mediated by these cells was not reversed by cytokine neutralization and was cell-cell contact-dependent. However, suppression of proliferation and IL-2 production by PItol cells in vivo was abrogated by neutralization of IL-10. These results emphasize an important role for IL-10 in the function of peptide-induced regulatory T cells in vivo and highlight the caution required in extrapolating mechanisms of T regulatory cell function from in vitro studies.
Sundstedt
Anette
A
Department of Pathology and Microbiology, University of Bristol Medical School, Bristol, United Kingdom. anette.sundstedt@activebiotech.com
O'Neill
Emma J
EJ
Nicolson
Kirsty S
KS
Wraith
David C
DC
D000281:Administration, Intranasal; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D005452:Fluoresceins / Q000378:metabolism; D006131:Growth Inhibitors / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000502:physiology*; D013388:Succinimides / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D005452:Fluoresceins; D006131:Growth Inhibitors; D007376:Interleukin-2; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D013388:Succinimides; C074815:myelin basic protein 1-9; D016753:Interleukin-10