Interleukin 12 breaks ultraviolet light induced immunosuppression by affecting CD8+ rather than CD4+ T cells.
Recent studies showed that injection of interleukin (IL)-12 prevents ultraviolet (UV) light mediated suppression of contact hypersensitivity and breaks UV-induced hapten specific tolerance. UV-mediated suppression can be adoptively transferred by injecting splenocytes from UV-irradiated mice; however, suppression is not transferable when donor mice are treated with IL-12 after UV-irradiation. This study was performed to elucidate the mechanisms by which IL-12 counteracts this immunosuppression. To characterize the cells transferring suppression, depletion studies were performed revealing that UV-induced suppression is transferred via CD8+ T cells. To investigate whether IL-12 counteracts UV-induced suppression by either inhibiting the development of CD8+ suppressor T cells or inducing CD4+ effector T cells, splenocytes from mice, which were IL-12 treated and sensitized through UV-exposed skin, were depleted from CD4+ T cells and transferred into naive mice that were subsequently sensitized. Whereas transfer of splenocytes from UV-irradiated mice inhibited sensitization of recipients, no inhibition was observed after transfer of splenocytes from UV-exposed and IL-12 treated mice. Recipients that received CD4 depleted spleen cells from UV-exposed and IL-12 treated donors, were still fully sensitizable. IL-12 also blocked transfer of UV-induced suppression when it was injected into UV-exposed donor animals at a time point when suppressor cells had already developed. CD4 depletion of such splenocytes did not result in a loss of the reconstitutive effect of IL-12. This suggests that IL-12 may break UV-induced tolerance not by inducing CD4+ effector T cells, but rather by inhibiting or inactivating suppressor T cells belonging to the CD8 subtype.
Schwarz
A
A
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, Germany.
Grabbe
S
S
Mahnke
K
K
Riemann
H
H
Luger
T A
TA
Wysocka
M
M
Trinchieri
G
G
Schwarz
T
T
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000528:radiation effects* / Q000637:transplantation; D003877:Dermatitis, Contact / Q000517:prevention & control; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects; D007165:Immunosuppression Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D014466:Ultraviolet Rays
D018664:Interleukin-12