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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)555-564
Number of pages10
JournalJournal of Clinical Investigation
Volume107
Issue number5
StatePublished - Mar 21 2001

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Autoantigens
Antigen-Presenting Cells
Thymus Gland
Class 8 Receptor-Like Protein Tyrosine Phosphatases
Insulin
Self Tolerance
Glutamate Decarboxylase
Tissue Distribution
Spleen
Lymphocytes
Phenotype
Protein Tyrosine Phosphatases
Type 1 Diabetes Mellitus
Dendritic Cells
Transgenic Mice
Lymph Nodes
Macrophages
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)

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Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. / Pugliese, Alberto; Brown, Douglas; Garza, David; Murchison, Djanira; Zeller, Markus; Redondo, Maria; Diez, Juan; Eisenbarth, George S.; Patel, Dhavalkumar D.; Ricordi, Camillo.

In: Journal of Clinical Investigation, Vol. 107, No. 5, 21.03.2001, p. 555-564.

Research output: Contribution to journalArticle

Pugliese, A, Brown, D, Garza, D, Murchison, D, Zeller, M, Redondo, M, Diez, J, Eisenbarth, GS, Patel, DD & Ricordi, C 2001, 'Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs', Journal of Clinical Investigation, vol. 107, no. 5, pp. 555-564.
Pugliese, Alberto ; Brown, Douglas ; Garza, David ; Murchison, Djanira ; Zeller, Markus ; Redondo, Maria ; Diez, Juan ; Eisenbarth, George S. ; Patel, Dhavalkumar D. ; Ricordi, Camillo. / Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 5. pp. 555-564.
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