Upregulation of Cytotoxic T-cells in pediatric patients with Gaucher disease

Abstract

Cytotoxic (CD8) T-cells and natural killer (NK) cells have a significant immune function role. The ongoing stimulation of immunity and the excessive release of proinflammatory cytokines observed in pediatric patients with Gaucher disease (GD) can affect immune cells. Few studies have looked at the proportion of cytotoxic CD8 T-cells and their subsets in children with GD. A prospective case–control study was performed involving twenty pediatric patients with type 1 GD and twenty healthy age-matched controls. All patients received regular enzyme replacement therapy (ERT) for at least 6 months before the study. Complete blood count and flow cytometric analyses of CD8 T, Tc1, Tc2, NK, and NK T-cells were performed. GD patients showed significantly increased of CD8 T, Tc1 and significantly decreased NK cells frequencies when compared to healthy controls. However, no significant difference in Tc2 and NK T-cells was found between the studied groups. GD patients on regular ERT have increased CD8+ T-cell frequencies, predominantly Tc1, together with a reduction in NK cells than in healthy controls. These crucial immunological changes may contribute to some extent to the pathogenesis and the progression of GD.

Leukocyte Imbalances in Mucopolysaccharidoses Patients

“…A reduction in NK cells had already been described in patients with other LSDs such as Gaucher disease [ 38 , 39 ] and Niemann–Pick disease type C1 [ 40 ] and could potentially be due to a decrease in shingosine-1-phosphate (S1P) gradients and to defects in calcium storage. Monocytes were also decreased in Fabry disease patients’ blood, which could be related to an increase in extravasation processes with higher migration to peripheral tissues, since monocytes overexpress CD31, a molecule implied in extravasation processes [ 41 ].…”

Age-related changes in the parameters of cellular immunity, the activity of intracellular lymphocyte dehydrogenases and functional activity of neutrophils in children with Gaucher disease

“…У детей с БГ отмечено значимое повышение цитотоксических Т-лимфоцитов в 1-й, 2-й и 5-й возрастных группах. В остальных группах также наблюдалась подобная тенденция, что согласуется с данными A.M. Zahran и подтверждает участие данной популяции в патогенезе БГ [13]. Помимо этого, выявлено снижение доли Т-хелперов во 2-й и…”

“…в сторону провоспалительных цитокинов и развитие хронического воспаления с вовлечением всех иммунных клеток, что может приводить к изменению состава как основных, так и малых популяций лимфоцитов [12]. Так, на выборке из 20 пациентов с БГ показано увеличение доли цитотоксических Т-клеток и снижение NK-клеток по сравнению со здоровыми людьми, данный факт авторы связывают с участием данных популяций в патогенезе и прогрессировании БГ [13]. Помимо этого, показано, что, несмотря на ФЗТ, Т-хелперы и B-регуляторные клетки у пациентов с БГ значительно снижены по сравнению с контрольной группой [14].…”

Immunosenescence, aging and successful aging

“…Tc cells (also known as killer T cells), expressing the CD8 surface marker, are crucial in immune defense against harmful pathogens by secreting cytotoxic substances such as granzyme and perforin ( 103 ). As people get older, Tc cell proliferation is impaired along with the decreased naive cell marker (CD45RA and CD27), the lymphocyte adhesion molecule SELL (CD62L) and the lymphoid tissue homing chemokine receptor (CCR7), while the expression of memory cell marker CD45RO and the senescent marker CD57 increase ( 104 ).…”