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The Anergic State in Sarcoidosis Is Associated with Diminished Dendritic Cell Function¹

Sneha Mathew^*, Kristy L. Bauer^*, Arne Fischoeder, Nina Bhardwaj^* and Stephen J. Oliver^2,*

^* Department of Medicine, New York University School of Medicine, New York, NY 10016; and University of Berlin (Charité), Berlin, Germany

Sarcoidosis is a chronic inflammatory disease of unknown cause, characterized by granuloma formation similar to tuberculosis, but without clear evidence of a microbial infection. Because sarcoidosis is linked with clinical anergy and other evidence of diminished cellular immunity, we hypothesized that decreased skin delayed-type hypersensitivity (DTH) responses to recall Ags in affected individuals would be associated with decreased function of their blood dendritic cells (DCs). Our study involved ex vivo isolation, phenotyping, and functional testing of myeloid DCs (mDCs), plasmacytoid DCs, and T lymphocytes from blood of normal healthy volunteers and sarcoidosis subjects with active, untreated pulmonary disease. We found mDC function in the allogeneic MLR directly corresponded to the magnitude of skin DTH reactions to recall Ags in both sarcoidosis subjects and normal volunteers. However, both of these outcomes were significantly decreased in the sarcoidosis group. Diminished mDC function occurred despite up-regulated costimulatory and maturation markers. Clinical relevance is suggested by the inverse relationship between both mDC allogeneic responses and skin DTH responses with clinical disease severity as measured by chest radiograms. Because granulomas form when cellular immunity fails to clear antigenic stimuli, attenuated mDC function in sarcoidosis may contribute to susceptibility and persistence of the chronic inflammation characteristic of this disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Institutes of Health grants, including HL077461 (to S.J.O.), and in part by the New York University School of Medicine General Clinical Research Centers Grant M01 RR-00096 from the National Center for Research Resources.

² Address correspondence and reprint requests to Dr. Stephen J. Oliver, Department of Medicine, NBV16N-1, New York University School of Medicine, 550 First Avenue, New York, NY 10016. E-mail address: stephen.oliver{at}med.nyu.edu

³ Abbreviations used in this paper: DTH, delayed-type hypersensitivity; DC, dendritic cell; lin^–, lineage-negative; mDC, myeloid dendritic cell; Mo-DC, dendritic cell derived in vitro from monocyte precursors; pDC, plasmacytoid dendritic cell.

This article has been cited by other articles:

				C. D. Becker and A. S. Teirstein Comment on "The Anergic State in Sarcoidosis Is Associated with Diminished Dendritic Cell Function" J. Immunol., April 1, 2009; 182(7): 3943 - 3943. [Full Text] [PDF]

				S. J. Oliver Response to Comment on "The Anergic State in Sarcoidosis Is Associated with Diminished Dendritic Cell Function" J. Immunol., April 1, 2009; 182(7): 3943 - 3943. [Full Text] [PDF]