Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines.
Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris. Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris. Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites of SEA. Mutations in only one of the two MHC class II binding sites of SEA has different effects on T-cell activation. Thus, SEA molecules with a mutation in the MHC class II beta-binding site induce protein tyrosine phosphorylation, but not IFN-gamma production or co-stimulation of cytokine-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites are involved in the autopresentation of SEA by psoriatic T cells. In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris.
Nielsen
M B
MB
Institute for Microbiology and Immunology, University of Copenhagen, Denmark.
Odum
N
N
Gerwien
J
J
Svejgaard
A
A
Bendtzen
K
K
Bregentholt
S
S
Röpke
C
C
Geisler
C
C
Dohlsten
M
M
Kaltoft
K
K
D000938:Antigen-Presenting Cells; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation; D004768:Enterotoxins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011565:Psoriasis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; C026066:enterotoxin A, Staphylococcal; D014443:Tyrosine; D007371:Interferon-gamma