Nitcheu Josianne, Bonduelle Olivia, Combadiere Christophe, Tefit Maurel, Seilhean Danielle, Mazier Dominique, Combadiere Behazine
Institut National de la Santé et de la Recherche Médicale, Unité 511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitie-Salpétrière, Université Pierre et Marie Curie, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
J Immunol. 2003 Feb 15;170(4):2221-8. doi: 10.4049/jimmunol.170.4.2221.
Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA infection involves T lymphocytes. However, the mechanisms of T cell-mediated pathogenesis remain unknown. We found that, in contrast to ECM-susceptible C57BL6 mice, perforin-deficient (PFP-KO) mice were resistant to ECM in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes and massive accumulation of activated/effector CD8 lymphocytes were observed in both groups of mice. ECM is induced in PFP-KO mice after adoptive transfer of cytotoxic CD8+ cells from infected C57BL6 mice, which were directed to the brain of PFP-KO mice. This specific recruitment might involve chemokine/chemokine receptors, since their expression was up-regulated on activated CD8 cells, and susceptibility to ECM was delayed in CCR5-KO mice. Thus, lymphocyte cytotoxicity and cell trafficking are key players in ECM pathogenesis.
由伯氏疟原虫ANKA感染引起的实验性脑型疟疾（ECM）涉及T淋巴细胞。然而，T细胞介导的发病机制仍不清楚。我们发现，与易患ECM的C57BL6小鼠不同，穿孔素缺陷（PFP-KO）小鼠在没有脑损伤的情况下对ECM具有抗性，而在两组小鼠中均观察到被寄生红细胞的细胞粘附以及活化/效应CD8淋巴细胞的大量积累。在用来自感染的C57BL6小鼠的细胞毒性CD8 +细胞过继转移至PFP-KO小鼠脑内后，PFP-KO小鼠诱发了ECM。这种特异性募集可能涉及趋化因子/趋化因子受体，因为它们在活化的CD8细胞上表达上调，并且CCR5-KO小鼠对ECM的易感性延迟。因此，淋巴细胞细胞毒性和细胞运输是ECM发病机制中的关键因素。
