PERIPHERAL-BLOOD LYMPHOCYTES FROM PSORIATIC PATIENTS ARE HYPORESPONSIVE TO BETA-STREPTOCOCCAL SUPERANTIGENS

The strong association of acute guttate psoriasis and streptococcal th roat infection, together with the preferential use of T cells expressi ng a particular T-cell receptor, has suggested a role for bacterial su perantigens in the pathogenesis of psoriasis. We examined the prolifer ative responses of peripheral blood lymphocytes (PBLs), obtained from patients with psoriasis and from healthy controls, to streptococcal su perantigens, cytoplasmic membrane-associated protein (CAP) and secreti on-type CAP (SCAP), isolated from group A, beta-haemolytic streptococc i. PBLs from patients with psoriasis showed significantly less respons e to SCAP and CAP than those from healthy controls. Because there was no difference between psoriatic patients and controls in the prolifera tive response of PBLs to staphylococcal enterotoxin A or E (SEA, SEE) or the mitogen phytohaemagglutinin (PHA), these findings strongly sugg est that the reduced reactivity to the streptococcal superantigens see ms 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 selectiv ely, we further examined the proliferation of V beta 8 T cells after s uch stimulation using flow cytometry. V beta 8 T cells obtained from t hree of four psoriatic patients failed to proliferate in the presence of CAP, whereas they proliferated vigorously in the presence of SEE, w hich activates V beta 8 T cells, confirming the specific hyporesponsiv eness of PBLs from psoriatic patients to streptococcal superantigens. We then determined the effects of serum factors on the suppressed resp onse of PBLs to the streptococcal superantigens with SCAP or CAP. It w as partially restored when PBLs were cultured with sera obtained from healthy subjects, although the responses were still significantly lowe r than those of the healthy controls. In contrast, psoriatic sera mark edly suppressed the proliferative response of PBLs from healthy contro ls to CAP or SCAP, but showed no suppression of the proliferative resp onse of PBLs to SEA. Because these findings suggest the presence of sp ecific inhibitory factors in psoriatic sera, we examined whether the i nhibitory effect was caused by antisuperantigen antibody. However, no significant increase was detected in antibody titre to CAP in psoriati c sera, as has been noted in sera from patients with poststreptococcal glomerulonephritis. The present results show for the first time the h yporesponsiveness of PBLs to streptococcal superantigens and the prese nce of serum inhibitors that specifically inhibit T-cell response to t he superantigens in psoriatic patients. These findings suggest a patho logical role for streptococcal infections in the pathogenesis of psori asis.