RESUMEN
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.
Asunto(s)
Eliminación de Gen , Linfopenia/inmunología , Neutropenia/complicaciones , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Adulto , Anciano , Apoptosis , Proliferación Celular , Enfermedad Crónica , Femenino , Humanos , Interleucina-7/sangre , Linfopenia/etiología , Linfopenia/genética , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Acortamiento del TelómeroRESUMEN
BACKGROUND: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate the type of lymphopenia in patients undergoing thoracoscopic talc poudrage. METHODS: We have measured peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+, CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic T-lymphocytes, respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. RESULTS: Absolute peripheral blood lymphocyte count significantly decreased following thoracoscopic talc poudrage compared to baseline values (p=0.007). Similarly, peripheral blood CD3+, CD4+ and CD8+ lymphocyte counts significantly decreased compared to baseline (p=0.005, 0.02 and 0.03, respectively) with a more prominent reduction of CD3/CD45RO memory cells. No significant difference was found in the absolute number of CD19+, CD16+, CD56+, and CD57+ cells before and after thoracoscopic talc poudrage. CONCLUSION: Patients undergoing thoracoscopic talc poudrage display peripheral blood T-lymphopenia following the procedure.