Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells.
We have recently demonstrated that a single dose (200 J/m2) of UVB radiation abrogates the capacity of mouse epidermal Langerhans cells (LC) or splenic adherent cells (SAC) to present keyhole limpet hemocyanin (KLH) to Ag-specific, MHC-restricted CD4+ Th1 cells. In the present study we determined whether such Th1 unresponsiveness represented long-lasting immunologic tolerance. To address this question, Th1 were preincubated with KLH-pulsed UVB-LC or UVB-SAC, then isolated and restimulated with unirradiated APC (LC or SAC) plus KLH or with exogenous rIL-2 in the absence of APC. Preincubation with KLH and UVB-LC or UVB-SAC rendered Th1 unresponsive to subsequent restimulation with APC and KLH. In addition, such Th1 were defective in their autocrine IL-2 production, but could respond normally to exogenous rIL-2, indicating that unresponsiveness was due to functional inactivation and not to cell death. Th1 unresponsiveness was Ag-specific, MHC-restricted, and long lasting (greater than 16 days). In addition, it appears that Th1 unresponsiveness is not due to the release of soluble suppressor factors from UVB-LC or UVB-SAC because supernatants from such cells had no effect on Th1 proliferation. Addition of unirradiated allogeneic SAC during preincubation prevented the induction of unresponsiveness by UVB-LC or UVB-SAC, suggesting that UVB interferes with the capacity of LC or SAC to deliver a costimulatory signal(s) that can be provided by allogeneic SAC. We conclude that UVB can convert LC or SAC from immunogenic to tolerogenic APC.
Simon
J C
JC
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235.
Tigelaar
R E
RE
Bergstresser
P R
PR
Edelbaum
D
D
Cruz
P D
PD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000528:radiation effects*; D007376:Interleukin-2 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays
D007376:Interleukin-2