T Lymphocyte Maturation Is Impaired in Healthy Young Individuals Carrying Trisomy 21 (Down Syndrome)

Abstract

Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7 concentration were examined in 24 youngsters with Down syndrome and no acquired diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a complex immune and impairment is present in healthy individuals with Down syndrome in whom interferon gamma, interleukin (IL) IL-10 production, as well as serum IL-7 concentrations and activation markers-bearing T lymphocytes were significantly augmented. Additionally, a complex skewing of post-thymic lymphocyte maturation pathways was observed in patients: significant reduction of CD4+ and CD8+ naive (RA+CCR7+) lymphocytes, significant increase of CD4+ and CD8+ central memory (RA-CCR7+), and terminally differentiated (TD) (RA+CCR7-) lymphocytes.

Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

“…Alteration in the immune system, such as functional and morphological thymus abnormalities (Bloemers et al, 2011;Karl et al, 2012), lymphocytopenia, and alteration in differentiation, maturation, and activation of the T lymphocyte (Guazzarotti et al, 2009;Lorenzo et al, 2013) is frequently observed in DS individuals (Kusters et al, 2009). It can be responsible for increased incidence of infections, mainly in the respiratory tract (Bloemers et al, 2010;Broers et al, 2012), and occurrence of autoimmune disease in DS (Gillespie et al, 2006;Pellegrini et al, 2012).…”

“…The cytokines belong to a diversified group of protein, which participated in various biological processes, including the mediation of the inflammatory response (Zhang and An, 2007). Changes in the concentration of proinflammatory and anti-inflammatory cytokines in DS individuals demonstrate its association with the syndrome pathogenesis (Tsilingaridis et al, 2003;Guazzarotti et al, 2009;Cetiner et al, 2010;Broers et al, 2012Broers et al, , 2014. The study of Cetiner et al (2010) observed that the IL6 serum levels were lower in DS children compared with individuals without the syndrome.…”

“…Furthermore, an increase in the production of alpha-TNF, beta-IL1, -IL6, -IL8, alpha-INF, gamma-INF, and IL10 was observed in peripheral blood culture of DS children, stimulated by influenza A virus and by Streptococcus pneumoniae (Broers et al, 2012(Broers et al, , 2014. A significant increase in IL7 serum levels in healthy adolescents with DS was observed, and peripheral blood mononuclear cells from these individuals stimulated with phytohemagglutinin (PHA) and cytomegalovirus (CMV) presented an increase of gamma-IFN and IL10 levels (Guazzarotti et al, 2009). The increase of the beta-IL1, -IL4, -IL6, -IL10, -IL12, gamma-IFN, and alpha-TNF levels and cytokines produced by T-helper cells (Th1, Th2, and Th17) was also observed in gingival crevicular fluid of DS adolescents compared with individuals without DS (Tsilingaridis et al, 2012).…”

“…Research in DS has shown that the 21 trisomy is associated with a reduction of T and B cells, alteration in differentiation and maturation of B cells, and activation of the Th1 and Th2 cells (Guazzarotti et al, 2009;Carsetti et al, 2015;Schoch et al, 2017). DS also present functional and morphological alterations of the thymus that is smaller (Kusters et al, 2009;Lorenzo et al, 2013), possibly as a result of the increase of cytokines as gamma-interferon (gamma-IFN), and tumor necrosis factor (alpha-TNF) (Murphy et al, 1992).…”

Unusual Detection of Tuberculosis in a Woman with Down's Syndrome

“…Immunological investigation of a small number of DS patients with tuberculosis (TB) has shown no consistent defect [7]. The immune cellular status in children with DS is similar to that of the normal population as far as white blood cell, lymphocyte, CD4(+), CD8(+), natural killer and immunoglobulins are concerned [8], and maturation of T lymphocytes may be impaired in healthy young individuals with DS [9]. Although common, illness in people with intellectual disabilities may be under diagnosed and poorly managed [10].…”