Peterson L D, van der Keur M, de Vries R R, Roep B O
Department of Immunohaematology, University Hospital Leiden, The Netherlands.
Diabetologia. 1999 Apr;42(4):443-9. doi: 10.1007/s001250051177.
AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease. Several subsets of T-cells, in particular CD4+ and in vivo activate CD45RA+RO+ T-cells, have been shown to be increased at disease onset. The functional implications of these relative increases in CD4 T-cells were investigated.
Subsets of T-cells were sorted on the basis of their activation status (CD45RA+ naive cells, CD45RA+RO+ recently activated cells and CD45RO+ memory cells) and stimulated with autoantigens or recall antigen in vitro.
Proliferative responses to tetanus toxoid were primarily or exclusively observed in resting memory T-cells (CD45RO+). Autoimmune T-cell responses were, however, primarily measured in activated T-cells (CD45RA+RO+) in newly diagnosed Type I diabetic patients, whereas those with longer disease duration reacted to autoantigens with memory T-cells (CD45RO+) (p < 0.004). Interestingly, in non-diabetic control subjects not responding to autoantigens in the regular assay, considerable autoreactive T-cell responses were detectable after sorting in the CD45RO+ or CD45RA+RO+ lymphocyte subsets. Remixing these subsets showed that these autoimmune responses in activated cells could be down-modulated by CD45RA+ lymphocytes, whereas resting memory cells appeared unaffected by the suppressive CD45RA subset.
CONCLUSION/INTERPRETATION: These results show that autoimmune T-cell responses can be linked to particular subsets which differ depending on clinical status. Furthermore, the CD45RA T-cell subset harbours lymphocytes potentially capable of suppressing autoimmune T-cell responses. The changes in responsiveness to exogenous insulin may help to unravel the mechanism by which isohormonal therapy could prevent the onset of Type I diabetes.
目的/假设：I型（胰岛素依赖型）糖尿病是一种T细胞介导的自身免疫性疾病。已显示几种T细胞亚群，特别是CD4+以及体内活化的CD45RA+RO+ T细胞，在疾病发作时会增加。对这些CD4 T细胞相对增加的功能影响进行了研究。
根据T细胞的活化状态（CD45RA+初始细胞、CD45RA+RO+近期活化细胞和CD45RO+记忆细胞）对T细胞亚群进行分选，并在体外用自身抗原或回忆抗原进行刺激。
对破伤风类毒素的增殖反应主要或仅在静止记忆T细胞（CD45RO+）中观察到。然而，在新诊断的I型糖尿病患者中，自身免疫性T细胞反应主要在活化T细胞（CD45RA+RO+）中检测到，而病程较长的患者对自身抗原的反应是记忆T细胞（CD45RO+）（p<0.004）。有趣的是，在常规检测中对自身抗原无反应的非糖尿病对照受试者中，在分选CD45RO+或CD45RA+RO+淋巴细胞亚群后可检测到相当数量的自身反应性T细胞反应。将这些亚群重新混合显示，活化细胞中的这些自身免疫反应可被CD45RA+淋巴细胞下调，而静止记忆细胞似乎不受抑制性CD45RA亚群的影响。
结论/解读：这些结果表明，自身免疫性T细胞反应可与取决于临床状态的特定亚群相关联。此外，CD45RA T细胞亚群含有可能能够抑制自身免疫性T细胞反应的淋巴细胞。对外源胰岛素反应性的变化可能有助于揭示等激素疗法预防I型糖尿病发作的机制。
