Blockade of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) down-regulates induction of contact sensitivity by haptenated epidermal cells.
The hapten, trinitrobenzene sulphonic acid, induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of hapten-treated epidermal cells induced hapten-specific contact sensitivity in synergic mice. Cells of the keratinocyte cell line, Pam 212, or epidermal cells treated with a mixture of anti-Ia/thy1.2/gamma delta antibody plus complement, did not show any sensitizing ability. When hapten-treated epidermal cells were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction, a reduction which was similar to that seen with the anti-ICAM-1 and anti-LFA-1 antibody-induced inhibition of contact sensitivity. Anti-B7-1 (CD80) or anti-B7-2 (CD86) antibody also inhibited hapten-specific lymphocyte proliferation or the allogenic mixed lymphocyte and epidermal cell reaction in vitro, although the inhibitory effect of anti-B7-1 antibody was not as significant as that of anti-B7-2 antibody. These results indicate that costimulatory signals induced by a hapten on epidermal Langerhans cells play an important role in the induction of hapten-specific contact sensitivity in mice.
Katayama
I
I
Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.
Matsunaga
T
T
Yokozeki
H
H
Nishioka
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D003877:Dermatitis, Contact / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006241:Haptens; D007801:Langerhans Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006241:Haptens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid