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Self-antigen–presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs
Alberto Pugliese, … , Dhavalkumar D. Patel, Camillo Ricordi
Alberto Pugliese, … , Dhavalkumar D. Patel, Camillo Ricordi
Published March 1, 2001
Citation Information: J Clin Invest. 2001;107(5):555-564. https://doi.org/10.1172/JCI10860.
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Article Article has an altmetric score of 9

Self-antigen–presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs

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Abstract

Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the thymus. The reported modulation of diabetes susceptibility by genetically determined differences in thymic insulin levels and studies in transgenic mice provide correlative and functional evidence that thymic expression of peripheral proteins is crucial for immunological self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express insulin and other self-antigens in the human thymus. We find that the human thymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla, and we demonstrate such cells also in peripheral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages. These cells often appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existence of, and define the tissue distribution and phenotype of, a novel subset of APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.

Authors

Alberto Pugliese, Douglas Brown, David Garza, Djanira Murchison, Markus Zeller, Maria Redondo, Juan Diez, George S. Eisenbarth, Dhavalkumar D. Patel, Camillo Ricordi

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Figure 2

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Self-antigen–expressing cell phenotype in thymus. Frozen thymus sections...
Self-antigen–expressing cell phenotype in thymus. Frozen thymus sections were subject to double immunofluorescence. Left column: double-stained cells exhibiting both TRITC (or Alexa-568) and FITC fluorescence often seen as variable gradations of yellow fluorescence with the tripleband filter. Center and right columns: staining for either one of the two individual markers used, as indicated above each image, using highly selective band pass filters for either TRITC (or Alexa-568) or FITC. Top to bottom: Proinsulin-CD83, case 1897. ×84. Not all cells are double stained. Proinsulin-CD11c, case 3446. ×140. Proinsulin-CD14, case 1829. ×90. Proinsulin-CD8α, case 3446. ×90. Proinsulin-AIRE, case 3446. ×90. The AIRE staining was specifically blocked with the peptide used to raise the rabbit serum. Color differences in the images showing the proinsulin staining (center panels) are due to the use of different conjugates (TRITC for the CD83 and CD14 series and Alexa-568 for the CD11c, CD8α, and AIRE series).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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