B7‐1 expression of Langerhans cells is up‐regulated by proinflammatory cytokines, and is down‐regulated by interferon‐γ or by interleukin‐10

Abstract

Langerhans cells (LC) act as potent antigen-presenting cells (APC) for primary and secondary T cell-dependent immune responses. LC express several costimulatory and/or adhesion molecules such as B7/BB1, which has been implicated as one of the important determinants for professional APC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7-1, B7-2, and B7-3. We have examined the regulatory properties of B7-1 expression in LC using various cytokines including interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon (IFN)-gamma, granulocyte/macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha. We have demonstrated: 1) that the B7-1 expression of LC is reproducibly up-regulated by either GM-CSF, TNF-alpha, IL-1 alpha, IL-1 beta, or IL-4 in a dose- and time-dependent manner, 2) that GM-CSF exhibits the most active effect on B7-1 up-regulation in each experiment, 3) that IFN-gamma or IL-10 profoundly inhibits the B7-1 expression of LC in a dose- and time-dependent manner, and 4) that the down-regulatory ability of IFN-gamma or IL-10 neutralizes the activity of up-regulatory cytokines. The enhancing or inhibitory action of these cytokines on B7-1 expression occurs selectively because none of the cytokines consistently affects I-A expression of LC. These data suggest that the B7-1 expression of LC may be dynamically regulated by these up- and down-regulatory cytokines in normal and inflammatory epidermal microenvironment.

Granulocyte/Macrophage Colony-Stimulating Factor Inhibits IL-12 production of Mouse Langerhans Cells

“…A similar result was observed in 48 h-cultured LC (data not shown). The expression of B7 molecules is known to be involved in immunostimulatory functions of LC (6). Our result is consistent with the previous report (6) and supports the concept that GM-CSF is a major factor for functional maturation of LC.…”

“…The expression of B7 molecules is known to be involved in immunostimulatory functions of LC (6). Our result is consistent with the previous report (6) and supports the concept that GM-CSF is a major factor for functional maturation of LC. In addition, we studied the effect of GM-CSF (1 ng/ml) on other cell surface molecules of 48-h cultured LC, such as I-A d , CD44, CD11c, NLDC 145, and CD14.…”

“…Specific skin inflammation, such as contact hypersensitivity and skin graft rejection, is regulated by a complex and sequential mechanism involving LC, keratinocytes (KC), T cells, and a variety of cytokines they produce (2)(3)(4). These cytokines are also known to modulate the function, morphology, and phenotype of LC (5,6), including Ag processing and presenting capacity, expression of cell surface molecules, and cytokine secretion.…”

Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

“…Expression of GM-CSF is required to allow for allergic mucosal sensitization, because exposure to OVA alone induces inhalation tolerance, as we and others have previously shown (15,16). Importantly, GM-CSF on its own does not elicit airway eosinophilia (12); hence, its effects are likely due to its adjuvant-like properties (17)(18)(19)(20)(21)(22)(23). After 2 wk of exposure, we observed marked eosinophilia in the bronchoalveolar lavage (BAL), resolved after 4 wk.…”

Combined suicide and granulocyte–macrophage colony-stimulating factor gene therapy induces complete tumor regression and generates antitumor immunity

“…GM -CSF has several functions, which promote the generation of an immune response, including the activation and expansion of neutrophils, monocytes, and dendritic cells, 44,45 and the up-regulation of cell surface co-stimulatory molecules required for T-cell activation. 46,47 As HSV1 -TK ± and GCV-mediated tumor cell lysis releases tumor antigens, we propose that the presence of GM -CSF in the tumor microenvironment enhances antigen uptake and presentation by APCs. This results in the generation of antitumor immunity, which enhances tumor regression and protects against recurrence.…”