T-cell activation is potentiated by cytokines released by lesional psoriatic, but not normal, epidermis.
METHODS
T-cell activation appears to be critical for the maintenance of psoriatic lesions. In this study, we determined whether cytokines released by epidermal cells from psoriatic lesions are providing signals that result in propagation of intralesional T-cell activation. Supernatants were obtained from epidermal cell cultures derived from skin biopsy specimens of psoriatic patients and normal subjects. These supernatants were added to purified normal CD4+ T cells activated via T-cell receptor (immobilized anti-CD3 and fibronectin) or via other activating pathways (anti-CDw60 or UM4D4).


RESULTS
Psoriatic supernatants (n = 9), but not normal supernatants (n = 7, P < .0006), potentiated T-cell stimulation with anti-CD3 and fibronectin to 172% +/- 41% over control stimulation levels. The degree of lesional psoriatic epidermal cell potentiation correlated with the clinical severity of the lesion (r = .82, P = .007). Psoriatic epidermal cytokine potentiation of T-cell activation was not limited to T-cell receptor mediated stimulation; potentiation of anti-CDw60-stimulated CD4+ T cells was also observed. Neutralizing antisera to interleukin 1 and interleukin 8, but not interleukin 6, were found to reduce only partly the observed potentiation of T-cell activation. To determine whether cyclosporine is down modulating T-cell-potentiating cytokine activity in psoriasis, we compared samples obtained during a double-blind clinical trial of intralesional cyclosporine. T-cell-potentiating activity from psoriatic lesional sites treated with cyclosporine was not significantly modulated relative to the activity derived from vehicle-treated or untreated sites.


CONCLUSIONS
These data demonstrate that lesional psoriatic epidermal cells release a balance of cytokines that potentiate T-cell activation. Because normal epidermal cells do not potentiate T-cell activation in this system, these findings demonstrate a mechanism by which the epidermis may non-specifically potentiate and perpetuate T-cell activation in psoriatic lesions.
Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0530.
E Y
EY
Chang
C
C
Hammerberg
G
G
Fisher
O
O
Baadsgaard
C N
CN
Ellis
J J
JJ
Voorhees
K D
KD
Cooper
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D005353:Fibronectins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D016572:Cyclosporine