4.5 Article

Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 10, Pages 2896-2904

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200838342

Keywords

Apoptosis; Dendritic cells; SLE; Tolerance

Categories

Funding

  1. Israeli Chief Scientist
  2. Israeli Academy of Sciences

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Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. in this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, age- and gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5% +/- 36.8% (p < 0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6% +/- 18.0% (p < 0.03). A significant (> 20%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cell acquisition was 70.0% +/- 24% (p < 0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.

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