The autologous mixed epidermal cell-T lymphocyte reaction is elevated in psoriasis: a crucial role for epidermal HLA-DR+/CD1a- antigen-presenting cells.
The objective of this study was to determine whether epidermal cells (EC) from psoriasis lesions and uninvolved skin could stimulate autologous T lymphocytes in the in vitro autologous mixed epidermal cell-T lymphocyte reaction (autologous MECLR). The functional role of antigen-presenting cell (APC) subsets was concurrently determined in this reaction. Mononuclear cells and purified T lymphocytes from peripheral blood of psoriasis patients showed a clear proliferative response to autologous unpurified epidermal cells from involved as well as uninvolved skin. The autologous mixed leukocyte reaction (MLR) was not elevated in psoriasis patients. In healthy controls and contact allergy patients, T-lymphocyte proliferation was not observed either in the autologous MECLR or in the autologous MLR. The level of proliferation in the autologous MECLR from psoriasis patients correlated to the number of epidermal cells that were added. To exclude the possibility that the observed proliferation in the autologous MECLR in psoriasis was due to the presence of epidermal T lymphocytes that were being stimulated and expanded in vitro, the stimulator EC were gamma irradiated (30 Gy) in some experiments. Preincubation of EC with cyclosporin A (CsA) significantly inhibited the autologous MECLR. The CsA-induced inhibition could be neutralized by the addition of fresh untreated EC to these cultures. This indicated that one of the modes of action of CsA in resolving psoriasis is, as some investigators have already shown, via inhibition of epidermal accessory cell function. In the autologous MECLR, APC from psoriasis skin could initiate this reaction, whereas APC from peripheral blood could not. This occurred in an MHC class II restricted fashion. Depletion experiments showed that Langerhans cells (HLA-DR+/CD1a+) were not the principal stimulators of autologous T lymphocytes in the MECLR. These results indicated that mainly HLA-DR+/CD1a- epidermal cells from psoriasis patients could stimulate autologous peripheral blood T lymphocytes in an MHC class II-restricted fashion.
Prens
E P
EP
Department of Dermatology, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Benne
K
K
van Joost
T
T
Benner
R
R
D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology*; D018949:Antigens, CD1; D003524:Cyclosporins / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D007801:Langerhans Cells / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011565:Psoriasis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018949:Antigens, CD1; D003524:Cyclosporins; D006684:HLA-DR Antigens