Abnormal lymphocyte function following long-term PUVA therapy for psoriasis

Abstract

The surface markers and function of peripheral blood lymphocytes were examined in patients on long-term therapy with methoxsalen and UV-A radiation (PUVA). Ten patients with psoriasis were selected because they had received a high exposure to PUVA therapy, i.e., more than 200 treatments over 2-6 years with cumulative exposure doses of 1700-6000 J/cm2 UV-A radiation. Results were compared to those obtained with lymphocytes from untreated patients and UV-B treated patients with psoriasis. The PUVA-treated patients had low levels of E rosette-forming cells in the peripheral blood and markedly impaired lymphocyte responses following stimulation with optimal and suboptimal doses of mitogens. The sensitivity of lymphocytes to in vitro treatment with PUVA was similar in the three groups of patients. The results of this study indicate that long-term PUVA therapy alters the function and cell-surface markers or distribution of lymphocytes.

PUVA suppresses the expression of cell adhesion molecules of lymphocytes

“…It has already been reported that PUVA therapy downregulates the immune response both in vivo (2)(3)(4)(5)(6)(8)(9)(10) and in vitro (7). We demonstrated here that PUVA therapy not only downregulates T-cell function but also suppresses the expression of cell adhesion molecules of T lymphocytes in vitro.…”

“…One of the therapeutic effects of PUVA on psoriasis vulgaris appears to be the inhibition of cell rephcation by the photoconjugation of psoralens with DNA of epidermal keratinocytes and dermal cells including endothelial cells (1). On the other hand, effects of PUVA therapy on circulating lymphocytes have also been indicated; namely, reduction in the numbers of circulating Erosette-forming lymphocytes (2), improvement of T-cell levels assessed by E-rosettes (3,4) and reduction in the number of circulating helper/inducer T cells (OKT4) (5). PUVA also inhibits DNA synthesis of circulating lymphocytes in vivo (6), and reduces cell-mediated immune responses (7) and delayed cutaneous hypersensitivity (2,(8)(9)(10).…”

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.…”

Photoimmunology

“…12, 13 These patients have been reported to have decreased immunization rates to contact allergens, 14, 15 and reduced numbers of circulating peripheral blood CD4 + T-cells. 16, 17 …”