LOW EXPRESSION OF CD40 AND B7 ON MACROPHAGES INFILTRATING UV-EXPOSED HUMAN SKIN - ROLE IN IL-2R-ALPHA(-) T-CELL ACTIVATION

After UV exposure of skin, epidermal Langerhans cells (LC) are deplete d, whereas CD11b(+) CD36(+) CD1a(-) monocytes/macrophages (UV-M Phi) i nfiltrate. Different immunological outcomes in vivo are mediated by LC (sensitization) and UV-M Phi (tolerance) which may be related to the distinct T cell activation states that these antigen-presenting cells (APC) induce. We previously demonstrated that CD4(+) T lymphocytes act ivated by UV-M Phi, are, in contrast to LC-activated T cells, IL-2R al pha deficient, and we hypothesize that this differential T cell activa tion is related to differences in co-stimulatory molecules between UV- M Phi and LC. Using four-color flow cytometry, we found a reduced capa city to up-regulate expression of the important co-stimulatory molecul es CD40, B7-1 and B7-2 by UV-M Phi relative to LC. This alteration in co-stimulatory molecule expression was selective, because UV-M Phi exp ress equal levels of ICAM-1 and ICAM-3, and increased levels of LFA-1, relative to LC. After bidirectional signaling with T cells during all oantigen presentation, UV-M Phi still exhibited less CD40 and B7-1 tha n LC. Addition of IFN-gamma induced CD40 and B7-1 expression on UV-M P hi and restored IL-2R alpha expression on UV-M Phi-activated T cells b ut had no effect on IL-2R alpha on resting or LC-activated T cells. Th e restoration of IL-2R alpha expression on UV-M Phi-activated T cells by IFN-gamma was inhibited (67 %, p = 0.005) by addition of neutralizi ng anti-CD40. Therefore, differences in co-stimulatory molecule expres sion, in particular CD40, on UV-M Phi and LC are critical in determini ng the distinct T cell activation induced by these APC.