Kawikova Ivana, Leckman James F, Kronig Holger, Katsovich Lily, Bessen Debra E, Ghebremichael Musie, Bothwell Alfred L M
Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Biol Psychiatry. 2007 Feb 1;61(3):273-8. doi: 10.1016/j.biopsych.2006.06.012. Epub 2006 Sep 25.
Post-streptococcal autoimmune inflammation of basal ganglia was suggested to be an etiological factor in some cases of Tourette syndrome (TS). Since regulatory T (T reg) cells play a major role in preventing autoimmunity, we hypothesized that a defect in T reg cells may be present in children with TS. We also postulated that group A beta hemolytic streptococcal infections could promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic exotoxins [SPE]).
We analyzed peripheral blood of TS patients and healthy age-matched control subjects by fluorescence-activated cell sorting (FACS) on multiple occasions and determined the numbers of CD4(+)CD25(+)CD69(-) T reg cells. Further, we quantified the number of CD4(+) and CD8(+) lymphocytes with regard to Vbeta chains to which SPEs are known to bind.
A significant decrease in T reg cells was observed in patients with moderate to severe TS symptoms compared with healthy age-matched control children. A decrease in T reg cell number was also noted during symptom exacerbations in five out of six patients. Further, we found a significant decrease in numbers of CD8(+)Vbeta18(+) T cells in moderate to severe TS patients.
These data support our hypothesis that at least some TS patients may have a decreased capacity to inhibit autoreactive lymphocytes through a deficit in T reg cells. Interactions of host T cell immunity and microbial factors may also contribute to the pathogenesis of TS.
有研究提示，基底节的链球菌感染后自身免疫性炎症是部分抽动秽语综合征（TS）病例的病因。鉴于调节性T（Treg）细胞在预防自身免疫中起主要作用，我们推测TS患儿可能存在Treg细胞缺陷。我们还推测，A组β溶血性链球菌感染可能通过释放外毒素（链球菌致热外毒素[SPE]）促进自身免疫反应。
我们多次采用荧光激活细胞分选术（FACS）分析TS患者及年龄匹配的健康对照者的外周血，测定CD4(+)CD25(+)CD69(-) Treg细胞数量。此外，我们对已知可与SPE结合的Vβ链相关的CD4(+)和CD8(+)淋巴细胞数量进行了定量分析。
与年龄匹配的健康对照儿童相比，中重度TS症状患者的Treg细胞显著减少。在6例患者中的5例症状加重期间，也观察到Treg细胞数量减少。此外，我们发现中重度TS患者的CD8(+)Vβ18(+) T细胞数量显著减少。
这些数据支持了我们的假设，即至少部分TS患者可能因Treg细胞缺陷而抑制自身反应性淋巴细胞的能力下降。宿主T细胞免疫与微生物因素的相互作用也可能参与了TS的发病机制。
