Thymic function in MHC class II–deficient patients

Background MHC class II (MHC-II) molecules play a pivotal role in the development, activation, and homeostasis of CD4+ TH cells in the thymus. The absence of MHC-II molecules causes severe T-cell immunodeficiency. Objective We sought to study thymic function, including T-cell receptor excision circl...

Full description

Saved in:
Bibliographic Details
Published in:Journal of allergy and clinical immunology 2013-03, Vol.131 (3), p.831-839
Main Authors: Lev, Atar, MSc, Simon, Amos J., BSc, Broides, Arnon, MD, Levi, Jacob, MD, Garty, Ben Zion, MD, Rosenthal, Ester, MSc, Amariglio, Ninette, PhD, Rechavi, Gideon, MD, PhD, Somech, Raz, MD, PhD
Format: Article
Language:English
Subjects:
Adult
Allergy and Immunology
Biological and medical sciences
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cytomegalovirus
Deoxyribonucleic acid
Disease
DNA
Flow cytometry
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Histocompatibility Antigens Class II - immunology
Humans
Immune system
immunodeficiency
Immunopathology
Infant
Leukocytes, Mononuclear - cytology
Lymphocytes
Medical sciences
MHC class II
neonatal screening
Patients
Receptors, Antigen, T-Cell - genetics
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
severe combined immunodeficiency
Severe Combined Immunodeficiency - genetics
Severe Combined Immunodeficiency - immunology
T cell receptors
T-cell receptor excision circle (TREC)
T-cell receptor repertoire
Thymus Gland - immunology
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background MHC class II (MHC-II) molecules play a pivotal role in the development, activation, and homeostasis of CD4+ TH cells in the thymus. The absence of MHC-II molecules causes severe T-cell immunodeficiency. Objective We sought to study thymic function, including T-cell receptor excision circle (TREC) quantification, in patients with MHC-II deficiency. Methods Eight MHC-II–deficient patients underwent a thorough T-cell immunologic work-up, including thymic activity, which was estimated based on TREC levels and T-cell receptor (TCR) genes, as well as analysis of several sequential human TCR gene rearrangements. Results In vitro responses to mitogens were normal or only slightly reduced, and flow cytometric evaluations of the TCR-Vβ repertoires of total CD3+ lymphocytes were normal in all patients. However, both the flow cytometric evaluation of the TCR-Vβ repertoire on CD4+ cells and spectratyping evaluation of the TCR-Vγ repertoire on total CD3+ lymphocytes showed clonal abnormalities. TRECs were present in all patients in both total lymphocytes and sorted CD4+ cells. Additionally, TRECs were detected in genomic DNA obtained from Guthrie cards with dried blood spots. Quantitative RT-PCR assessment of different TCR gene rearrangement events revealed lower levels in MHC-II–deficient patients compared with levels seen in healthy control subjects. This was irrespective of the total lymphocyte numbers, suggesting a reduced global thymic activity. Conclusions Our report highlights potential pitfalls in diagnosing MHC-II deficiency and emphasizes the probable importance of MHC-II molecules in the normal thymic maturation process of T cells. Patients with MHC-II deficiency have detectable TRECs and might therefore be missed by a TREC-based newborn screening program.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2012.10.040