Alveolar Macrophages in Sarcoidosis Coexpress High Levels of CD86 (B7.2), CD40, and CD30L

Nicod, Laurent P.; Isler, Patrick

doi:10.1165/ajrcmb.17.1.2781

Cited by 65 publications

(49 citation statements)

References 20 publications

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“…With regard to IL-12 production in APCs, not only LPS stimulation but also the interaction between CD40 and CD40 ligand are important (33). Significantly enhanced expression of CD40 was observed in alveolar macrophages of sarcoid cases compared with that in normal alveolar macrophages (34). The interaction of CD40 and CD40 ligand may be a clue to the greater induction of IL-12 p70 in sarcoid BAL fluid cells than in normal BAL fluid cells.…”

Section: Discussionmentioning

confidence: 98%

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

Shigehara

Shijubo²,

Ohmichi

et al. 2001

The Journal of Immunology

167

101

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Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-γ production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-γ, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-γ induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-γ and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-γ production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-γ production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-γ production, indicating important cytokines in the Th1 response of sarcoidosis.

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Section: Discussionmentioning

confidence: 98%

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

Shigehara

Shijubo²,

Ohmichi

et al. 2001

The Journal of Immunology

167

101

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“…Our data are supported by several reports. Cells isolated by BAL from human patients with inflammatory lung disease that were cytologically classified as alveolar macrophages have been shown to function similar to DCs because the cells were capable of inducing T cell responses (28,29). Inflammatory stimuli have been shown to induce activation of alveolar macrophages (38,39) in mice and inhibit their immunosuppressive activity (30).…”

Section: Discussionmentioning

confidence: 99%

IL-13 Regulates the Immune Response to Inhaled Antigens

Padilla

Daley

Chow

et al. 2005

The Journal of Immunology

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The large inhibitory effect of IL-13 blockers on the asthma phenotype prompted us to ask whether IL-13 would play a role in regulating the allergic immune response in addition to its documented effects on structural pulmonary cells. Because IL-13 does not interact with murine T or B cells, but with monocytes, macrophages, and dendritic cells (DCs), we examined the role of IL-13 in the activation of pulmonary macrophages and DCs and in the priming of an immune response to a harmless, inhaled Ag. We found that a majority of cells called “alveolar or interstitial macrophages” express CD11c at high levels (CD11chigh) and are a mixture of at least two cell types as follows: 1) cells of a mixed phenotype expressing DC and macrophage markers (CD11c, CD205, and F4/80) but little MHC class II (MHC II); and 2) DC-like cells expressing CD11c, CD205, MHC II, and costimulatory molecules. Endogenous IL-13 was necessary to induce and sustain the increase in MHC II and CD40 expression by pulmonary CD11chigh cells, demonstrated by giving an IL-13 inhibitor as a measure of prevention or reversal to allergen-primed and -challenged mice. Conversely, IL-13 given by inhalation to naive mice increased the expression of MHC II and costimulatory molecules by CD11chigh cells in an IL-4Rα-dependent manner. We found that exogenous IL-13 exaggerated the immune and inflammatory responses to an inhaled, harmless Ag, whereas endogenous IL-13 was necessary for the priming of naive mice with an inhaled, harmless Ag. These data indicate that blockade of IL-13 may have therapeutic potential for controlling the immune response to inhaled Ags.

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“…In two studies using AM isolated by BAL and evaluated by flow cytometry, normal AM were reported to be B7-1 ¹ and weakly positive for B7-2, and the expression of these costimulatory molecules was not increased by culture in the presence of IFN-g [14,15]. From these results, the authors suggested that the poor ability of AM to serve as accessory cells for antigen-induced T cell proliferation is due to defective expression of B7 molecules.…”

Section: Discussionmentioning

confidence: 99%

In situexpression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas

Stolzmann

Boussaud

Moreau

et al. 1999

Clinical and Experimental Immunology

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SUMMARYNormal alveolar macrophages (AM) are not efficient in inducing the proliferation of resting T lymphocytes, and, rather, tend to inhibit pulmonary immune responses. In contrast, epithelioid cells (EC), activated macrophages that play an essential role in the course of granulomatous responses, appear to stimulate T cell proliferation efficiently. The inability of macrophages to deliver potent costimulatory signals through the B7/CD28 and CD40/CD40L pathways could explain their weak accessory cell activity. Using MoAbs and immunohistochemical techniques, however, we found that essentially all AM in normal human lung tissue expressed B7-1, B7-2 and CD40 molecules, and most of these cells were strongly positive. Pulmonary macrophages in other compartments also expressed these costimulatory molecules; no differences in expression were observed comparing macrophages from smokers and non-smokers. Most AM recovered by bronchoalveolar lavage from normal lung segments also strongly expressed B7-1, B7-2 and CD40 molecules. In comparison, resting blood monocytes were B7-1 ¹ and only moderately positive for B7-2. Activation of monocytes with lipopolysaccharide (LPS) induced expression of these costimulatory molecules to levels similar to that of AM from the control subjects. EC in granulomatous lesions also expressed easily detectable levels of B7-1, B7-2 and CD40. T lymphocytes within and surrounding the granulomas expressed CD28, the counter-receptor for B7, and many of these T cells also expressed B7-1 and B7-2. These findings suggest that both AM and EC can deliver costimulatory signals through B7-1, B7-2 and CD40 molecules, and indicate that the impairment in accessory cell activity observed for normal AM cannot be attributed to the absence of expression of these costimulatory molecules.

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Alveolar Macrophages in Sarcoidosis Coexpress High Levels of CD86 (B7.2), CD40, and CD30L

Cited by 65 publications

References 20 publications

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

IL-12 and IL-18 Are Increased and Stimulate IFN-γ Production in Sarcoid Lungs

IL-13 Regulates the Immune Response to Inhaled Antigens

In situexpression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas

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