Perforin-Dependent Brain-Infiltrating Cytotoxic CD8+ T Lymphocytes Mediate Experimental Cerebral Malaria Pathogenesis

• Published in: The Journal of immunology (1950) 2003-02, Vol.170 (4), p.2221-2228
• Main Authors: Nitcheu, Josianne, Bonduelle, Olivia, Combadiere, Christophe, Tefit, Maurel, Seilhean, Danielle, Mazier, Dominique, Combadiere, Behazine
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Brain - immunology; Brain - metabolism; Brain - parasitology; Brain - pathology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Movement - genetics; Cell Movement - immunology; Female; Fluoresceins - metabolism; Genetic Predisposition to Disease; Immunity, Innate - genetics; Immunologic Memory - genetics; Malaria, Cerebral - genetics; Malaria, Cerebral - immunology; Malaria, Cerebral - pathology; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Perforin; Plasmodium berghei - immunology; Plasmodium berghei - pathogenicity; Pore Forming Cytotoxic Proteins; Receptors, CCR5 - biosynthesis; Receptors, CCR5 - deficiency; Receptors, CCR5 - genetics; Spleen - chemistry; Spleen - cytology; Spleen - immunology; Spleen - transplantation; Succinimides - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - pathology
• ISSN: 0022-1767; 1550-6606
• 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.