Unit of Experimental Medicine, Christian de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Exp Hematol. 2011 Jun;39(6):676-85. doi: 10.1016/j.exphem.2011.03.002. Epub 2011 Mar 11.
Immunization of normal CBA mice with rat platelets leads to an autoantibody response directed against mouse platelets. The purpose of this work was to determine the involvement of T lymphocytes in this response.
T-lymphocyte responses were analyzed in vivo by depletion and transfer experiments and ex vivo by proliferation assay and cytokine measurements.
Mouse immunization with rat platelets induced production of antibodies reacting with rat and mouse platelets. This response was found to depend on CD4(+) T-helper lymphocytes reacting with rat, but not with mouse platelets. These anti-rat platelet T-helper cells were mainly of the Th1 phenotype. When transferred into naïve mice, they enhanced the anti-mouse platelet antibody response induced by subsequent immunization with rat platelets. In addition, depletion of CD25(+) cells enhanced the thrombocytopenia induced by immunization with rat platelets, whereas adoptive transfer of CD4(+)CD25(+) cells from immunized mice suppressed it.
Our results suggest that activation of anti-rat platelet T-helper cells can bypass the mechanism of tolerance and result in the secretion of autoreactive antibodies, but this response is still controlled by regulatory T cells that develop progressively after immunization.
用大鼠血小板对正常 CBA 小鼠进行免疫接种会导致针对小鼠血小板的自身抗体反应。本研究的目的是确定 T 淋巴细胞在此反应中的参与情况。
通过耗竭和转移实验在体内分析 T 淋巴细胞反应,并通过增殖测定和细胞因子测量在体外分析 T 淋巴细胞反应。
用大鼠血小板对小鼠进行免疫接种会诱导产生与大鼠和小鼠血小板反应的抗体。结果发现,该反应依赖于与大鼠而非小鼠血小板反应的 CD4(+)T 辅助性淋巴细胞。这些抗大鼠血小板 T 辅助细胞主要为 Th1 表型。当转移到未致敏的小鼠中时,它们增强了随后用大鼠血小板免疫接种诱导的抗小鼠血小板抗体反应。此外,耗竭 CD25(+)细胞增强了用大鼠血小板免疫接种引起的血小板减少症,而从免疫小鼠中过继转移 CD4(+)CD25(+)细胞则抑制了它。
我们的结果表明,激活抗大鼠血小板 T 辅助细胞可以绕过耐受机制并导致自身反应性抗体的分泌,但这种反应仍受到免疫后逐渐产生的调节性 T 细胞的控制。