Is psoriasis induced by streptococcal superantigens and maintained by M-protein-specific T cells that cross-react with keratin?
The evidence that T lymphocytes play a key role in the pathogenesis of psoriasis is now compelling. Eruption of psoriatic skin lesions coincides with epidermal infiltration and activation of T cells, and spontaneous or treatment-induced resolution of the lesions is preceded by the reduction or disappearance of epidermal T cells. An upregulation has also been demonstrated for various molecules associated with T-cell mediated inflammation, and treatments selectively directed against T cells have proved very effective. Infections with group A beta-haemolytic streptococci have been associated with onset of acute psoriasis and exacerbation of chronic psoriasis. Such infections are also frequently accompanied by erythematous skin rashes. Also, recent reports indicate that streptococcal superantigens can induce expression of cutaneous lymphocyte antigens (CLA), believed to play a major role in enabling T cells to migrate to the skin. Furthermore, T-cell lines isolated from psoriatic lesions may show strong reactivity to streptococcal antigens. We have postulated that psoriasis is an autoimmune disease mediated by T cells reacting to epitopes that are common to streptococcal M-proteins and keratins. To investigate this possibility, circulating T cells from 12 patients with active psoriasis, paired controls, and six patients with atopic dermatitis were challenged in vitro with five synthetic 20aa (amino acid) M-peptides: production of IFN-gamma and IL-4 was analysed by ELISPOT and RT-PCR techniques. Four of these peptides shared five to six aa sequences with several type I keratins and one did not. In 10 of the 12 psoriasis patients, measurable IFN-gamma production could be induced by one or more of the four peptides that share sequences with keratins. A borderline response was observed in only four of the 18 controls: the dermatitis patients were all negative. The only peptide that shared 6aa with keratins was the one that induced a response in the psoriatic patients most frequently, and four of them showed the strongest response to this peptide while none of the controls reacted to it. In all instances negligible responses were observed to the control peptide that did not share sequences with keratins. Except for PHA-stimulated controls, IL-4 responses could not be detected by either ELISPOT or RT-PCR and there was generally good agreement between the two techniques. A marked reduction in the M-peptide-induced IFN-gamma responses was observed in the psoriasis patients during remission induced by UVB treatment, while their responses to streptokinase-streptodornase were not affected. Thus, active psoriasis is associated with a Th1 type response to short peptides with epitopes shared by streptococcal M-protein and keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein-specific Th1-like cells that cross-react with human epidermal keratin.
Valdimarsson
H
H
Department of Immunology, National University Hospital, Reykjavik, Iceland.
Sigmundsdóttir
H
H
Jónsdóttir
I
I
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007633:Keratins / Q000276:immunology*; D011565:Psoriasis / Q000209:etiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013291:Streptococcus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C014689:streptococcal M protein; D007633:Keratins