Publication: Sistemik lupus eritematozus’da CD8 + CD28 - supresör T hücreleri
Abstract
Sistemik Lupus Eritematosus (SLE), oto-antikor ve immün kompleks üretimiyle karakterize prototipik bir otoimmün hastalıktır. İmmün sistem hücrelerinin etkileşimlerindeki bozulmalar self-toleransın kaybına ve oto-antikor üretimine neden olmaktadır. CD8+CD28- fenotipindeki T hücre populasyonlarının antijen sunucu hücrelerle direkt kontağıyla ya da anti-inflamtuar sitokinler salgılayarak, yardımcı T hücrelerinin reaktivitelerini engelledikleri ve baskılayıcı mekanizmayı başlatarak B hücreleri tarafından oto-antikor üretiminin baskılayabilecekleri gösterilmiştir. Bu çalışmada 53 SLE hastasının periferik kan CD8+CD28- T hücre populasyonları sağlıklı bireyler ile karşılaştırılmıştır. SLE hastaları ve sağlıklı bireyler arasında total CD8 ve CD28 miktarlarında bir fark bulunmazken, CD8+ T hücrelerindeki CD28- populasyon dağılımı SLE hastalarında anlamlı olarak düşük bulunmuştur (Sırası ile %44±20, %58±13; p<0.01). Bununla beraber, SLE hastalarının CD8+ T hücrelerindeki CD28+ populasyonlarının dağılımı anlamlı olarak yüksek bulunmuştur (Sırası ile, %56±20, %42± 3; p<0.01). SLE hastalarının monositlerindeki kostimülatör molekül CD80 ve CD86 arasında fark bulunmazken SLE hastalarında sağlıklı bireylere oranla CD40 molekülünün anlamlı derecede düşük olduğu saptanmıştır (Sırası ile, %89±9, %74±17; p<0.01). Gruplar arasında CD8+ hücrelerce zenginleştirilmiş populasyonlardaki IL-10 seviyeleri arasında bir fark bulunmamıştır. CD8+CD28- ve CD28+CD28+ hücre populasyonları arasında perforin seviyesinde farka rastlanmamış; farklı PHA konsantrasyonundaki uyarımlar sonucunda ve zamanla CD8+CD28- populasyonunda miktar olarak bir değişim gözlemlenmemiştir. SLE hastalarının CD8+CD28- T hücrelerindeki azalma, T hücre baskılanmasında bir kusurun bulunduğunu ve otoreaktif B hücrelerine T hücre yardımını arttırdığını düşündürmektedir. CD8+CD28-, SUPPRESIVE, T CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of autoantibodies and immune complexes. Impaired interactions between immune cells including T cells, monocytes, dendritic cells and B cells lead to loss of self-tolerance and autoantibody production. Recently, it has been shown that a CD8+CD28- phenotype of T cell population inhibits the reactivity of T helper cells either by a contact dependent mechanism or with secreting anti-inflammatory cytokines, initiating a suppressive loop which results in suppression of antibody production by B cells. In this study, we have explored the peripheral blood CD8+CD28- T cell population in 53 patients with SLE in comparison to healthy controls. Although no difference in total CD8 and CD28 counts has been found, the percentage of CD28- cells within CD8+ population has been found significantly decreased in patients with SLE compared to healthy subjects (44%±20 vs 58%±13, respectively p<0.01). In contrast, the ratio of CD28+ population within CD8+ T cells were significantly increased in SLE group (56% ± 20 vs 42% ± 13, p<0.01). While there were no significant differences in the expression of co-stimulatory molecules CD80 and CD86, CD40 expression on monocytes was found significantly decreased in patients with SLE (89%±9 vs 74%±17, respectively p<0.01). No difference in IL-10 expressions in CD8+ enriched populations was observed in patients with SLE in comparison to healthy controls. Neither a discrepancy in perforin levels among CD8+CD28- vs CD28+CD28+ populations, nor a change in frequency of CD8+CD28- T cells has been observed after distinct concentrations of PHA stimulation and time. Decreased CD8+CD28- T cell population may reflect the impaired T cell suppression and increased T cell help to autoreactive B cells in SLE.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of autoantibodies and immune complexes. Impaired interactions between immune cells including T cells, monocytes, dendritic cells and B cells lead to loss of self-tolerance and autoantibody production. Recently, it has been shown that a CD8+CD28- phenotype of T cell population inhibits the reactivity of T helper cells either by a contact dependent mechanism or with secreting anti-inflammatory cytokines, initiating a suppressive loop which results in suppression of antibody production by B cells. In this study, we have explored the peripheral blood CD8+CD28- T cell population in 53 patients with SLE in comparison to healthy controls. Although no difference in total CD8 and CD28 counts has been found, the percentage of CD28- cells within CD8+ population has been found significantly decreased in patients with SLE compared to healthy subjects (44%±20 vs 58%±13, respectively p<0.01). In contrast, the ratio of CD28+ population within CD8+ T cells were significantly increased in SLE group (56% ± 20 vs 42% ± 13, p<0.01). While there were no significant differences in the expression of co-stimulatory molecules CD80 and CD86, CD40 expression on monocytes was found significantly decreased in patients with SLE (89%±9 vs 74%±17, respectively p<0.01). No difference in IL-10 expressions in CD8+ enriched populations was observed in patients with SLE in comparison to healthy controls. Neither a discrepancy in perforin levels among CD8+CD28- vs CD28+CD28+ populations, nor a change in frequency of CD8+CD28- T cells has been observed after distinct concentrations of PHA stimulation and time. Decreased CD8+CD28- T cell population may reflect the impaired T cell suppression and increased T cell help to autoreactive B cells in SLE.