Ultraviolet radiation-induced regulatory T cells not only inhibit the induction but can suppress the effector phase of contact hypersensitivity.
Epicutaneous application of haptens to UV-exposed skin induces hapten-specific tolerance. This is mediated via regulatory T cells (Tr), as i.v. injection of T cells from UV-tolerized mice into naive animals renders the recipients unresponsive to the respective hapten. However, when UV-induced Tr are injected i.v. into sensitized mice, contact hypersensitivity (CHS) is not suppressed, suggesting that Tr inhibit the induction, but not the elicitation, of CHS and are inferior to T effector cells. As sensitization takes place in the lymph nodes, but elicitation occurs in the area of challenge, we postulated that Tr injected i.v. locate to the lymph nodes and not to the periphery and therefore only suppress the induction, not the elicitation, of CHS. Indeed, i.v. injection of Tr into sensitized mice did not inhibit CHS, although injection of Tr into the ears of sensitized mice suppressed the challenge. Inhibition was hapten specific, as injection of dinitrofluorobenzene (DNFB)-specific Tr into the ears of oxazolone (OXA)-sensitized mice did not affect challenge with OXA. However, when ears of OXA-sensitized mice were injected with DNFB-specific Tr and painted with DNFB before OXA challenge, CHS was suppressed. Inhibition correlated with the local expression of IL-10. Depletion studies and FACS analysis revealed that Tr express the lymph node-homing receptor L-selectin, but not the ligands for the skin-homing receptors E- and P-selectin, suggesting that UV-induced Tr, although able to inhibit T effector cells, do not suppress the elicitation of CHS upon i.v. injection, because they obviously do not migrate into the skin.
Schwarz
Agatha
A
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Von Esmarchstrasse 58, D-48149 Münster, Germany.
Maeda
Akira
A
Wild
Martin K
MK
Kernebeck
Kerstin
K
Gross
Nicole
N
Aragane
Yoshinori
Y
Beissert
Stefan
S
Vestweber
Dietmar
D
Schwarz
Thomas
T
D019264:Adoptive Transfer; D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology* / Q000517:prevention & control*; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D004431:Ear, External; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D016130:Immunophenotyping; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D019041:L-Selectin / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010081:Oxazolone / Q000037:antagonists & inhibitors / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects* / Q000637:transplantation; D014466:Ultraviolet Rays
D006241:Haptens; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D010081:Oxazolone; D004139:Dinitrofluorobenzene