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TNF receptor distribution in human tissues

B Ryffel1, M J Mihatsch

  • 1Institut für Toxikologie, Eidgenössischen Technischen Hochschule, Universität Zürich, Switzerland.

International Review of Experimental Pathology
|January 1, 1993
PubMed
Summary

Tumor necrosis factor-alpha (TNF-alpha) receptors were located in lymphoid tissues, not non-lymphoid tissues. TNF-alpha may regulate immune responses via p55 and p75 receptors on lymphoid cells.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine in immune regulation.
  • Understanding TNF-alpha receptor distribution is crucial for elucidating its in vivo functions.

Purpose of the Study:

  • To investigate the cellular localization of TNF-alpha receptor (TNF-R) proteins (p75 and p55) in lymphoid tissues.
  • To determine the relationship between TNF-alpha production and receptor expression in immune responses.

Main Methods:

  • In situ immunohistochemistry using monoclonal antibodies against TNF-R p75 and p55.
  • Analysis of receptor expression in thymus, lymph nodes, and other secondary lymphoid tissues.
  • Assessment of species specificity of the antibodies.

Main Results:

  • TNF-R p75 was found on medullary lymphoblasts and dendritic cells in the thymus, and on activated lymphocytes and interdigitating reticulum cells in secondary lymphoid tissues.
  • TNF-R p55 was localized to germinal center dendritic reticulum cells, the primary site of TNF-alpha production.
  • Receptor expression and TNF-alpha levels were upregulated in reactive hyperplasia.
  • No TNF-R was detected in non-lymphoid tissues.
  • Antibodies showed high species specificity, cross-reacting with nonhuman primates but not rodents or dogs.

Conclusions:

  • TNF-alpha, produced by germinal center dendritic reticulum cells, may regulate immune responses via autocrine and paracrine pathways involving p55 and p75 receptors.
  • Differential expression of TNF-R subtypes suggests distinct roles in immune cell regulation within lymphoid tissues.

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