T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders : Current Opinion in Allergy and Clinical Immunology

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Primary immune deficiency disease: Edited by Amos Etzioni and Ramsey Fuleihan

T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders

Somech, Raz

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Current Opinion in Allergy and Clinical Immunology 11(6):p 517-524, December 2011. | DOI: 10.1097/ACI.0b013e32834c233a

Abstract

Purpose of review 

The thymus gland provides an environment for the production of rearranged diversified populations of T-cell receptors (TCRs) expressed on peripheral T cells. These receptors respond to nonself-antigens and are tolerant to self-antigens. During TCR rearrangement processes, unused excised DNA fragments create byproducts termed TCR excision circles (TRECs). Although these byproducts have no function, their detection in the peripheral blood stream is a clear indication that a rearrangement process has occurred. Their enumeration in the latest circle created during TCR delta deletion and the final TCR alpha rearrangement can determine thymus output.

Recent findings 

Since the first description of its monitoring changes in the frequency of recent thymic emigrants with age and in human immunodeficiency virus (HIV)1 infection, TREC assessments have been used in many clinical settings in which T-cell immunity is involved, including diagnosing, understanding and monitoring T-cell immunodeficiencies, HIV infection, aging, autoimmune diseases and immune reconstitution after bone marrow transplantation.

Summary 

Confounding factors, such as cell division, cell death, longevity of the naïve T cells, and intracellular degradation, are known to affect TREC levels, yet measurement of TREC content is still considered the most reliable tool for tracking recent thymic emigrants. Its recent implantation for neonatal screening to diagnose severe combined immunodeficiency by using dry blood spots from Guthrie papers makes TREC the most accurate noninvasive tool to detect T-cell immune disorders. Together with determination of the TCR repertoire, TREC contents can give a clear insight into peripheral T-cell homeostasis.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.

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