TCRV beta 7+ Th2 cells mediate UVB-induced suppression of murine contact photosensitivity by releasing IL-10.
In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.
Yagi
H
H
Department of Dermatology, Hamamatsu University School of Medicine, Japan.
Tokura
Y
Y
Wakita
H
H
Furukawa
F
F
Takigawa
M
M
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017454:Dermatitis, Photoallergic / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance / Q000528:radiation effects; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology; D018418:Th2 Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D014466:Ultraviolet Rays
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10