LOW-DOSE UVB RADIATION PERTURBS THE FUNCTIONAL EXPRESSION OF B7.1 ANDB7.2 COSTIMULATORY MOLECULES ON HUMAN LANGERHANS CELLS

In previous studies, we have shown that ultraviolet (UV) B radiation p erturbs the APC function of Langerhans cells (LC) by interfering with as-yet unidentified co-stimulatory signals. Recently, B7.1 and B7.2 on APC were shown to deliver important co-stimulatory signals through in teraction with their counterreceptors CD28 and CTLA-4 on T cells. To d etermine whether UVB affects the functional expression of B7.1 or B7.2 on LC, B7.1 and B7.2 expression was studied on human LC by multiparam eter flow cytometry. Little, if any, B7.1 or B7.2 was detected on LC f reshly isolated from skin. However, following 48 h of tissue culture, expression of both B7.1 and B7.2 were markedly up-regulated. To test w hether these molecules were functional, primary mixed epidermal cell l eukocyte reactions (MECLR) were performed. Blocking monoclonal antibod y (mAb) to B7.1 or B7.2 both inhibited the MECLR, with anti-B7.2 being much more effective than anti-B7.1. UVB radiation dose-dependently (1 00-200 J/m(2)) suppressed the culture-induced up-regulation of B7.1 an d B7.2 on LC. Since LC exposed to the same UVB flux (UVB-LC) failed to stimulate alloreactive T cells in a MECLR, we questioned whether this was related to their inability to provide B7 co-stimulation. Indeed, when effective B7-CD28 signaling was ascertained by adding submitogeni c doses of exogenous anti-CD28 mAb to UVB-LC, the proliferative respon se of alloreactive T cells was restored. We conclude that the suppress ive effects of low-dose UVB radiation on the APC function of LC are, a t least in part, due to an inhibition of functional B7.1 and B7.2 expr ession.