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

Publication ,  Journal Article
Pugliese, A; Brown, D; Garza, D; Murchison, D; Zeller, M; Redondo, MJ; Diez, J; Eisenbarth, GS; Patel, DD; Ricordi, C
Published in: J Clin Invest
March 2001

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.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 2001

Volume

107

Issue

5

Start / End Page

555 / 564

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Self Tolerance
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Proinsulin
  • Phenotype
  • Middle Aged
  • Membrane Proteins
 

Citation

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Pugliese, A., Brown, D., Garza, D., Murchison, D., Zeller, M., Redondo, M. J., … Ricordi, C. (2001). Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest, 107(5), 555–564. https://doi.org/10.1172/JCI10860
Pugliese, A., D. Brown, D. Garza, D. Murchison, M. Zeller, M. J. Redondo, J. Diez, G. S. Eisenbarth, D. D. Patel, and C. Ricordi. “Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs.J Clin Invest 107, no. 5 (March 2001): 555–64. https://doi.org/10.1172/JCI10860.
Pugliese A, Brown D, Garza D, Murchison D, Zeller M, Redondo MJ, et al. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest. 2001 Mar;107(5):555–64.
Pugliese, A., et al. “Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs.J Clin Invest, vol. 107, no. 5, Mar. 2001, pp. 555–64. Pubmed, doi:10.1172/JCI10860.
Pugliese A, Brown D, Garza D, Murchison D, Zeller M, Redondo MJ, Diez J, Eisenbarth GS, Patel DD, Ricordi C. Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. J Clin Invest. 2001 Mar;107(5):555–564.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 2001

Volume

107

Issue

5

Start / End Page

555 / 564

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Self Tolerance
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Proinsulin
  • Phenotype
  • Middle Aged
  • Membrane Proteins