Lymphopenia in patients with chronic idiopathic neutropenia is associated with decreased number of T-lymphocytes containing T-cell receptor excision circles

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Abstract

Objectives:

Chronic idiopathic neutropenia (CIN) is a disorder of granulopoiesis characterized by the presence of activated T-lymphocytes that induce/sustain apoptosis of bone marrow (BM) granulocytic progenitors. T-cell lymphopenia is commonly found in CIN. The aim of the study is to probe the mechanisms underlying T-cell lymphopenia in CIN.

Methods:

We investigated parameters of T-cell homeostasis namely the proliferation/apoptotic rate of naïve and memory T cells, the T-cell senescence by telomere measurement, the recent thymic T-cell production through quantification of T-cell receptor rearrangement excision circles (TRECs), and the production of interleukin (IL)-7.

Results:

Patients with CIN (n = 44) displayed lower proportion of naïve CD45RA+ cells within the CD4+ and CD8+ cells compared with controls (n = 15). The proportion of apoptotic cells within the CD8+ fraction was higher in patients compared with controls and was correlated with the percentage of Ki-67+ cells, indicating an activation-induced accelerated CD8+ cell death. The TREC content of CD4+ and CD8+ cells was lower in patients compared with controls and was correlated with the proportion of CD45RA+ CD4+ and CD8+ cells and with the levels of serum and BM IL-7, which were significantly decreased in the patients. The mean relative telomere length of CD4+ and CD8+ cells was significantly lower in patients with CIN compared with age-matched controls.

Conclusions:

The aberrant T-cell expansions associated with the pathogenesis of CIN result in increased proliferation/apoptosis and possibly exhaustion of peripheral blood T cells which, in association with the inadequate compensatory thymic export of new TREC expressing T cells partially because of IL-7 deficiency, may contribute to lymphopenia in CIN.

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