SELECTIVE INACTIVATION OF LYMPHOCYTES AFTER PSORALEN ULTRAVIOLET-LIGHT (PUVA) TREATMENT WITHOUT AFFECTING SYSTEMIC IMMUNE-RESPONSES

Psoralens, together with ultraviolet light A (PUVA), are used for the treatment of several proliferative diseases. It has been suggested tha t the effectiveness of this treatment is due to induction of a specifi c immune response by PUVA-treated lymphocytes that down-regulates untr eated cells of the same specificity. The present studies show that the clinically used psoralen analogue 8-methoxypsoralen (8-MOP), as well as 4,8-dimethyl-5'-(pyridiniummethyl)psoralen bromide (4NQ), a derivat ive that does not cross; the cell membrane, when activated by UVA ligh t, render lymphocytes unresponsive to mitogenic, antigenic, or phorbol myristate acetate + ionomycin-induced stimulation. This state of unre sponsiveness was not reversed by exogenous recombinant interleukin-2. Treatment of lymphocytes with 4NQ and UVA light had no effect on the v iability or the homing pattern of the cells to spleen or liver, wherea s 8-MOP induced toxicity in about 50% of cells after 3 days in culture . Using an adoptive transfer mouse model, we found that antigen-specif ic lymphocytes treated with PUVA (8-MOP or 4NQ) had no effect on the a bility of these mice to respond to a subsequent challenge with the sam e or an irrelevant antigen. This was tested by measuring the T cell pr oliferative responses of lymph node cells from mice primed with keyhol e limpet hemocyanin (KLH) or fowl gamma globulin (FGG) before or after adoptive transfer of large numbers of KLH- or FGG-specific PUVA-treat ed lymph node cells. No effects of antigen-primed PUVA-treated cells o n antigen-primed untreated cells were observed in vitro in mixed lymph ocyte cultures responding to the relevant antigen. These results sugge st that, in our model system, PUVA induces cell inactivation but does not affect systemic T cell responses.