INHIBITION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTE FUNCTION BY PROTOPORPHYRIN AND LONGWAVE ULTRAVIOLET-LIGHT

Modulation of immunologic effector cells by exogenous photoactive subs tances has been advanced as an underlying mechanism for the efficacy o f various photochemotherapeutic regimens. It is also possible that end ogenous photosensitizers, such as protoporphyrin, could similarly modi fy the function of immune cell types. We examined the effects of proto porphyrin plus longwave UV light on the ability of human PBL to prolif erate in response to mitogens. Noncytotoxic dosages of protoporphyrin plus UV light suppressed PHA-stimulated proliferation of both PBMC and enriched T cells. CD8(+) cells were more sensitive to this inhibitory effect than CD4(+) cells. The inhibitory effect was also observed whe n proliferation was induced by the combination of a phorbol ester and ionomycin. Inhibition of PBMC proliferation was associated with inhibi tion of IL-2 secretion but proliferation was not restored with exogeno us IL-2. Instead, the effect of protoporphyrin plus UV light may be on IL-2R. Cells treated with protoporphyrin and UV light did not display the increase in CD25 and the beta-chain of the IL-2R induced by PHA i n control cells. In contrast to the effects of protoporphyrin and UV l ight on IL-2 and IL-2R alpha-chain protein expression, the accumulatio n of mRNA for these proteins induced by PHA was unaffected. None of th e effects of protoporphyrin plus UV light on lymphocytes were observed in control experiments where cells were treated with either protoporp hyrin or UV light alone. We conclude that biologically relevant dosage s of protoporphyrin and UV light modify the function of circulating ly mphocytes.