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Examination of Thymic Positive and Negative Selection by Flow Cytometry
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Thymic function in MHC class II-deficient patients.

Atar Lev1, Amos J Simon, Arnon Broides

  • 1Cancer Research Center, Jeffery Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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|December 12, 2012
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Summary
This summary is machine-generated.

MHC class II deficiency can be missed by newborn screening as patients have detectable T-cell receptor excision circles (TRECs). This highlights the critical role of MHC-II in normal T-cell maturation within the thymus.

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Area of Science:

  • Immunology
  • Genetics

Background:

  • MHC class II (MHC-II) molecules are crucial for CD4(+) T helper cell development and function in the thymus.
  • MHC-II deficiency leads to severe T-cell immunodeficiency.

Purpose of the Study:

  • To investigate thymic function in patients with MHC-II deficiency.
  • To assess T-cell receptor excision circle (TREC) levels as an indicator of thymic activity.

Main Methods:

  • Evaluated eight MHC-II-deficient patients with comprehensive T-cell immunologic work-up.
  • Quantified TRECs and analyzed T-cell receptor (TCR) gene rearrangements.
  • Assessed TCR repertoires using flow cytometry and spectratyping.

Main Results:

  • Patients exhibited clonal abnormalities in TCR-Vβ (CD4+ cells) and TCR-Vγ repertoires.
  • TRECs were detected in all patients, including on dried blood spots.
  • Quantitative RT-PCR showed reduced TCR gene rearrangement events, indicating diminished thymic activity.

Conclusions:

  • MHC-II deficiency diagnosis may be challenging due to detectable TRECs.
  • MHC-II molecules are vital for normal thymic T-cell maturation.
  • TREC-based newborn screening may miss patients with MHC-II deficiency.