Topical application of T-2 toxin inhibits the contact hypersensitivity response in BALB/c mice.
T-2 toxin, a trichothecene mycotoxin, has previously been shown to alter immune functions and promote skin tumors. We demonstrate that topically applied T-2 toxin reduces the ear swelling response to oxazolone challenge in BALB/c mice. For this reduction in ear swelling to occur, toxin application must be at, or within, 1 h after challenge. Dose-response studies showed a 44% reduction in ear swelling with 30 ng of T-2 toxin as compared with a similar reduction with 300 ng of dexamethasone. T-2 toxin did not affect Ag transport from the challenge site to the draining lymph nodes as measured by FITC transport. However, T-2 toxin significantly reduced both MHC class II (Ia) expression and Ag presentation at the same concentrations. Because T-2 toxin, a known protein synthesis inhibitor, was found to inhibit protein synthesis in epidermal cell cultures as measured by [3H]-leucine incorporation, cycloheximide was also examined. Cycloheximide reduced both oxazolone-induced ear swelling and Ag presentation in a similar manner to T-2 toxin. One mechanism of action for T-2 toxin in reducing the contact hypersensitivity response is via inhibition of protein synthesis and effective Ag presentation by epidermal Langerhans cells. This may involve alterations in Ia Ag expression, although a role for class II in the induction phase of the contact hypersensitivity response has not been established definitively.
Environmental Immunology Section, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709.
B L
BL
Blaylock
Y
Y
Kouchi
C E
CE
Comment
P L
PL
Pollock
M I
MI
Luster
D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007700:Kinetics; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000633:toxicity; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D013605:T-2 Toxin / Q000633:toxicity*
D000949:Histocompatibility Antigens Class II; D011500:Protein Synthesis Inhibitors; D010081:Oxazolone; D003513:Cycloheximide; D013605:T-2 Toxin