title: Epidermal CD8+ T cells in chronic plaque psoriasis are Tc1 cells producing heterogeneous levels of interferon-gamma.
abstract: The majority of epidermal CD8+ T cells in chronic plaque psoriasis are activated Tc1 cells producing interferon-gamma and no interleukin-4, a small proportion of which express NK-T receptors. To quantitate their level of cytokine production and characterize them further, CD8+ T cells were isolated from epidermal cell suspensions of lesional biopsies from 24 patients with chronic plaque psoriasis. T-cell lines (TCL) were established by culture of CD8+ T cells with feeders and IL-2 for 11 days and expansion with PHA. Ten TCL were stained for surface markers; 6 were cloned with PHA by limiting dilution. Interferon-gamma, interleukin-4 and interleukin-10 production was measured by ELISA after PMA/anti-CD3 activation of 15 TCL and 39 CD8+ T-cell clones. The 10 TCL stained were CD8alphabeta+ (93.3%), T-cell receptor-alphabeta+ (99.5%), costimulatory molecule CD28+ (90.1%), with a small CD8alphaalpha+ population (2.3%). No NK-T-cell receptor CD158a or CD158b expression was detected, whilst CD94 was expressed on 6.2% of cells in 6/9 TCL. All the TCL and 37/39 CD8+ T-cell clones produced interferon-gamma but no or minimal interleukin-4 or interleukin-10. The TCL produced a wide range of interferon-gamma levels (138 to 15,020 pg/ml). Clones from 3 patients showed low levels (60 to 1,410 pg/ml), from 2 patients high levels (6,105 to 43,040 pg/ml) and from 1 patient a wide range (405 to 36,010 pg/ml) of interferon-gamma production. Thus epidermal CD8+ Tc1 cells in chronic plaque psoriasis produce highly heterogeneous levels of interferon-gamma, which may reflect clinical diversity.
authors.affiliation: Dermatology Research, Imperial College of Science Technology and Medicine at St Mary's, Norfolk Place, London W2 1PG, UK. j.ovigne@ic.ac.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Ovigne
authors.forename: B S
authors.initials: BS
authors.lastname: Baker
authors.forename: D W
authors.initials: DW
authors.lastname: Brown
authors.forename: A V
authors.initials: AV
authors.lastname: Powles
authors.forename: L
authors.initials: L
authors.lastname: Fry
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma