Peripheral blood lymphocytes from psoriatic patients are hyporesponsive to β‐streptococcal superantigens

Abstract

The strong association of acute guttate psoriasis and streptococcal throat infection, together with the preferential use of T cells expressing a particular T-cell receptor, has suggested a role for bacterial superantigens in the pathogenesis of psoriasis. We examined the proliferative responses of peripheral blood lymphocytes (PBLs), obtained from patients with psoriasis and from healthy controls, to streptococcal superantigens, cytoplasmic membrane-associated protein (CAP) and secretion-type CAP (SCAP), isolated from group A, beta-haemolytic streptococci. PBLs from patients with psoriasis showed significantly less response to SCAP and CAP than those from healthy controls. Because there was no difference between psoriatic patients and controls in the proliferative response of PBLs to staphylococcal enterotoxin A or E (SEA, SEE) or the mitogen phytohaemagglutinin (PHA), these findings strongly suggest that the reduced reactivity to the streptococcal superantigens seems to reflect anergy of a population of PBLs to the superantigens. As the CAP used in the present study stimulates V beta 8 T cells selectively, we further examined the proliferation of V beta 8 T cells after such stimulation using flow cytometry. V beta 8 T cells obtained from three of four psoriatic patients failed to proliferate in the presence of CAP, whereas they proliferated vigorously in the presence of SEE, which activates V beta 8 T cells, confirming the specific hyporesponsiveness of PBLs from psoriatic patients to streptococcal superantigens. We then determined the effects of serum factors on the suppressed response of PBLs to the streptococcal superantigens with SCAP or CAP. It was partially restored when PBLs were cultured with sera obtained from healthy subjects, although the responses were still significantly lower than those of the healthy controls. In contrast, psoriatic sera markedly suppressed the proliferative response of PBLs from healthy controls to CAP or SCAP, but showed no suppression of the proliferative response of PBLs to SEA. Because these findings suggest the presence of specific inhibitory factors in psoriatic sera, we examined whether the inhibitory effect was caused by antisuperantigen antibody. However, no significant increase was detected in antibody titre to CAP in psoriatic sera, as has been noted in sera from patients with poststreptococcal glomerulonephritis. The present results show for the first time the hyporesponsiveness of PBLs to streptococcal superantigens and the presence of serum inhibitors that specifically inhibit T-cell response to the superantigens in psoriatic patients. These findings suggest a pathological role for streptococcal infections in the pathogenesis of psoriasis.

Incidence and Risk Factors for Psoriasis in the General Population

“…35,37,38 We found an increased risk of psoriasis in patients with recent infectious disease, and the risk was greater within the first month after an upper respiratory tract infection, in particular among individuals aged 21 to 40 years. We did not have valid information to study the specific underlying infectious agent.…”

Pediatric Psoriasis Revisited

“…Peripheral blood lymphocytes (Vb8 T cells) from psoriatic patients have been shown to be hyporesponsive to b-streptococcal superantigens. 34 A recent case-control study demonstrated that family history of psoriasis, stressful life events, and recent infectious diseases, particularly recent acute pharyngitis, are risk factors for a ®rst episode of AGP. 35 It is often recommended to treat AGP with penicillin or a cephalosporin, but the results have been inconsistent and the ef®cacy of antibiotics on the outcome of childhood AGP remains to be proven.…”

T helper 1 to T helper 2 shift in cytokine expression: an autoregulatory process in superantigen-associated psoriasis progression?

“…Thus, the regulatory T cell (Tr1) subset seems to play a profound downregulatory role in suppressing the potentially harmful Th1 immune response induced by superantigens (Cameron et al, 2001). T-cell deletion/anergy could also be a possible mechanism underlying repeated relapses, due to either superantigen stimulation or other factors leading to a significant decline in Th1 cytokines; hyporesponsiveness of PBMCs to the streptococcal superantigens reported in the past have been suggested to be due to T-cell anergy (Horiuchi et al, 1998).…”