Effect of 8-methoxypsoralen plus UVA (PUVA) on lymphocyte transformation and T cells in psoriatic patients

Abstract

The peripheral blood lympochytes of the psoriatic patients studied initially showed a normal response to phytohaemagglutinin (PHA) and to purified protein derivative of tuberculin (PPD) in a microculture using whole blood, but a lower than normal response to a high concentration of concanavalin A (Con A). The initial level of E-rosette-forming T cells in psoriatic patients (51 3%) was significantly lower than that in healthy controls (66 7/,,).A single exposure to 8-methoxypsoralen (8-MOP) and UVA light (PUVA) did not suppress the lymphocyte responses to PHA, Con A or PPD, rather the responses showed a tendency to be slightly increased. Sitnilarly, no changes in the mitogen responses of peripheral blood lymphocytes were recorded during or after 12 weeks PUVA therapy for psoriasis. The lymphocytes still showed a weaker than normal response to a high concentration of Con A. However, the percentage of E-rosette-forming T cells in the peripheral blood increased from 51*3% to 62-8% after 12 weeks PUVA therapy.The low initial level of E-rosette-forming T cells was found to correlate more closely with the activity than with the extent of the disease. The increase found in the E-rosette-forming cells during PUVA therapy did not correlate with the improvement of the psoriatic lesions. The low response of peripheral blood lymphocytes of psoriatic patients to a high concentration of Con A correlated with the age of the patients but not with the activity or extent of the disease.

PUVA Treatment Selectively Induces a Cell Cycle Block and Subsequent Apoptosis in Human T‐Lymphocytes

“…Many of the nonlethal immune-modulating effects, however, should be short-lived, suggesting that long-term benefits (months to years) derived from PUVA treatment of diseases such as psoriasis and CTCL m a y be based, instead, in the ability of P U V A to delete activated T-cell clones, which are preferentially located in the skin (24). In psoriasis, PUVA treatment depletes >90% of T-lymphocytes infiltrating cutaneous lesions (3), but comparatively small effects are produced o n circulating T-lymphocytes (25)(26)(27). Hence the ability of P U V A to deplete o r eliminate specific intracutaneous T-cell clones by direct cytotoxic actions may underlie its ability t o induce disease remissions in diseases such as psoriasis and CTCL.…”

Transient impairment of peripheral blood lymphocyte function during PUVA therapy

“…The effect of PUVA therapy on lymphocyte sub-populations has also been examined by several groups with a similar variation in the results. Fraki et al (1979) found that the proportion of circulating E-rosette-forming cells rose in a group of patients with psoriasis during a 12-week course of PUVA therapy. The mean result for the twelve patients was 51-3% before therapy and 62-8% after therapy, as compared to 667% in a healthy control group.…”

“…The results obtained in these studies have varied. The response of lymphocytes to stimulation by PHA was found not to alter during the course of PUVA therapy in three studies (Ortonne et al, 1978;Wassilew, 1978;Fraki, Eskola & Hopsu-Havu, 1979). Blood samples were obtained either immediately after or immediately before exposures to PUVA; in the latter case it is not possible to be certain of the time lapse after the last exposure to PUVA.…”

“…Blood samples were obtained either immediately after or immediately before exposures to PUVA; in the latter case it is not possible to be certain of the time lapse after the last exposure to PUVA. The methodology varied with the use of separated lymphocytes in one study (Wassilew, 1978) and whole blood in another study (Fraki et aL, 1979), while no details of the methodology were given in the third study (Ortonne et al, 1978). The response of lymphocytes to another mitogen, concanavalin A, was also found to be unchanged during a course of PUVA therapy for psoriasis (Franki et al, 1979).…”

An assessment of the effect of photo-chemotherapy (PUVA) and UV-B phototherapy in the treatment of psoriasis

“…However, the relevance of these experimental studies for the situation obtaining in PUVA treated psoriatic skin remains unclear. Although Kraemer & Weinstein (1977) reported a decrease in DNA synthesis in non-stimulated lymphocytes from PUVA treated patients and several authors have found a decrease in mitogen response in lymphocytes taken at various times during a course of PUVA therapy (Lischka et al, 1977;Morison et al, 1979b;Friedmann & Rogers, 1980), others have failed to detect any change (Ortonne et al, 1978;Wassilew, 1978;Fraki, Eskola & Hopsu-Havu, 1979;Harper et al, 1979), and also there is no increase in sister chromatid exchange rate in circulating blood cells from patients undergoing PUVA therapy (Wolff-Schreiner et al, 1977;Faed et al, 1980).…”