|
Yersinia enterocolitica 是腸內菌屬的一員, 人體被感染後會引發急性
腸胃炎,有些人隨後會有自體免疫疾病 (antoimmune disease) 的併發症
產生, 如雷氏症候群 (Reiter''s syndrome) 和反應性關節炎 (reactive
arthritis) 。反應性關節炎 (以下簡稱 ReA) 是一種無菌發炎性關節疾
病 (sterile inflammatory joint disease), 而且 ReA 通常是革蘭氏陰
性菌在引發腸胃道或泌尿生殖道感染後所引發的併發症之一 。由於 ReA
病人的關節腔中已証實有腸內菌物質 (enterobacterial materiails) 的
存在, 因此 ReA 的發生可能和關節中有微生物抗原 (microbial
antigens) 的存在有很重要的關係 。有些研究者認為 ReA 的發生和 Y.
enterocolitica 抗原所引發的細胞性免疫反應 (cellular immune
response) 有很密切的關係 。而另外一個假說是認為持續性的暴露在
"超抗原" (superantigen) 下有可能會引發自體免疫疾病, 更進一步的資
料顯示 Y. enterocolitica 和 Y. pseudotuberculosis 所製造的抗原性
物質帶有和超抗原相似的特性 。在本實驗中我們發現 Y.
enterocolitica 的培養上清液能引發 BALB/c, C57BL/6 和C3H/HeJ 小鼠
脾臟細胞的增殖, 接著我們用膠質過濾法 (gel filtration) 和離子交換
層析法 (ion-exchanger) 更進一步純離 Y. enterocolitica 的培養上清
液, 再用 SDS-PAGE 分析這些具有分裂素活性 (mitogenic activity) 的
分管後發現, 14 kDa 和 19 kDa 這兩個主要組成和分裂素活性的有無有
很大的關連 。 另外 Y. enterocolitica 的細胞質萃取物亦能刺激脾臟
細胞的增殖 。在體內實驗中, 以腹腔注射 (i.p.) 的方式給予C3H/HeJ小
鼠 Y. enterocolitica 的培養上清液濃縮物, 結果造成 C3H/HeJ 小鼠胸
腺萎縮和脾臟腫大, 而且發現胸腺細胞進行 apoptosis, 具有 DNA 片斷
化的現象 。另外用流體細胞分析儀分析的結果顯示, 胸腺的萎縮是因為
帶有 CD4+CD8+, Thy-1high 和 TCR-αβlow 這群胸腺細胞的減少, 但是
並沒有觀察到胸腺細胞帶有 Vβ 的族群有明顯的變化 。若給予 C3H/
HeJ 小鼠 LPS 則沒有胸腺細胞萎縮及細胞次族群減少的現象 。總而言
之, Y. enterocolitica 的培養上清液能刺激 LPS 低反應小鼠- C3H/
HeJ 的脾臟細胞增殖, 而且在體內實驗中將培養上清液濃縮物給予 C3H/
HeJ 小鼠會造成胸腺的萎縮和脾臟腫大 。
Yersinia enterocolitica is a member of the Enterobacteriaceae
family, and this organism causes acute gastroenteritis. One
complication of infection with Y. enterocolitica in man has
been the development of autoimmune disease, such as Reiter''s
syndrome and reactive arthritis (ReA). Some investigators
suggest that cellular immune response to antigens of Y.
enterocolitica play a role in the pathogenesis of ReA.
However, one current hypothesis suggests that one potential
consequence of exposure to superantigens is the development of
autoimmunity. Recent studies showed that Y. enterocolitica and
Y. pseudotuberculosis produced antigenic materials bearing
properties consistent with those of T cells superantigens. In
this study, we showed that the culture supernatant of Y.
enterocolitica could induce proliferation of splenocytes from
various strains of mice including BALB/c, C57BL/6 and C3H/HeJ.
The culture supernatant was chromatographed in gel filtration
and ion-exchange columns. SDS-PAGE analysis of the
mitogenically active fractions revealed that the fractions
contained two predominant bands corresponding to the molecular
mass of 14 kDa and 19 kDa. Besides, the cytosol extract of Y.
enterocolitica could also induce mouse splenocyte
proliferation. Furthermore, i.p. administration of
concentrated culture supernatant from Y. enterocolitica to C3H/
HeJ mice resulted in thymus atrophy and spleen enlargement. The
thymocytes underwent apoptosis as characterized by DNA
fragmentation. Using flow cytometric analysis, we further
showed that thymus atrophy was due maily to the deletion of
CD4+ CD8+, Thy-1high and TCR-αβlow cells, but there was no
significant changes in thymocyte subpopulations. In summary,
the culture supernatant of Y. enterocolitica could induce
splenocytes proliferation in vitro, and cause in vivo thymus
atrophy and spleen enlargement of LPS low-responder C3H/HeJ
mice.
|
