SELECTIVE REGULATION OF ICAM-1 AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II MOLECULE EXPRESSION ON EPIDERMAL LANGERHANS CELLS BY SOME OF THE CYTOKINES RELEASED BY KERATINOCYTES AND T-CELLS

Epidermal Langerhans cells (LC) are major histocompatibility complex (MHC) class II (Ia)-positive dendritic cells that act as potent antigen-presenting or accessory cells for primary and secondary T cell-dependent immune responses. Recent studies have disclosed that the morphological, functional, and phenotypic characteristics of LC are variably and drastically modulated by external stimuli both in vivo and in vitro. However, little is known of the biological significance of diverse cytokines in regulating the surface molecules of LC. To determine the regulatory properties of ICAM-1, Ia, and MHC class I (H-2K) molecules in LC, we have examined the effects of interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of these molecules. Among the cytokines examined, IFN-gamma markedly and reproducibly up-regulates the expression of H-2K, but not ICAM-1, in Ia(+) LC in a time- and dose-dependent manner. TNF-alpha consistently up-regulates the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 slightly but reproducibly inhibits the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 potently inhibits the TNF-alpha-induced ICAM-1 up-regulation, but not the IFN-gamma-induced H-2K up-regulation. Moreover, no cytokine consistently affects the Ia expression of LC. In addition, slight enhancing effects have been observed on H-2K expression by IL-4, and on ICAM-1 expression by IL-1 alpha, IL-1 beta, or GM-CSF. The present data suggest that the selective regulation is operative in a certain cell surface moiety of LC by various cytokines. These results further facilitate our understanding of immunobiology of LC.