The anergic state in sarcoidosis is associated with diminished dendritic cell function.
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.
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Sneha
S
Mathew
Kristy L
KL
Bauer
Arne
A
Fischoeder
Nina
N
Bhardwaj
Stephen J
SJ
Oliver
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D001772:Blood Cell Count; D001798:Blood Proteins / Q000378:metabolism; D002175:Candida / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D012507:Sarcoidosis / Q000276:immunology* / Q000378:metabolism / Q000601:surgery
D015415:Biomarkers; D001798:Blood Proteins; D016207:Cytokines; C453101:carboxyphenylglycine; D005998:Glycine