Cerebral malaria in mice - Interleukin-2 treatment induces accumulation ofgamma delta T cells in the brain and alters resistant mice to susceptible-like phenotype

In this study, we report that infection with Plasmodium yoelii 17XL, a leth al strain of rodent malaria, does not result in death in the DBA/2 strain o f mice. In contrast to BALB/c mice, DBA/2 mice developed significantly less parasitemia and never manifested symptoms of cerebral malaria (CM) on infe ction with this parasite. Moreover, the histological changes evident in the brain of susceptible BALB/c were absent in DBA/2 mice. Interestingly, the resistant DBA/2 mice when treated with recombinant interleukin (IL)-2, were found to develop CM symptoms and the infection became fatal by 6 to 8 days after infection. This condition was associated with an augmented interfero n-gamma and nitric oxide production. Unexpectedly, IL-10 levels were also e levated in IL-2-treated DBA/2 mice during late stage of infection (at day 6 of infection) whereas the inverse relationship between IL-10 and interfero n-gamma or nitric oxide was maintained in the early stage of infection (at day 3 after infection). The level of tumor necrosis factor-alpha production was moderately increased in the late phase of infection in these mice. His tology of brain from IL-2-treated mice demonstrated the presence of parasit ized erythrocytes and infiltration of lymphocytes in cerebral vessels, and also displayed some signs of endothelial degeneration. Confocal microscopic al studies demonstrated preferential accumulation of gamma delta T cells in the cerebral vessels of IL-2-treated and -infected mice but not in mice tr eated with IL-2 alone. The cells recruited in the brain were activated beca use they demonstrated expression of CD25 (IL-2R) and CD54 (intercellular ad hesion molecule 1) molecules. Administration of anti-gamma delta mAb preven ted development of CM in IL-2-treated mice until day 18 after infection whe reas mice treated with control antibody showed CM symptoms by day 6 after i nfection. The information concerning creating pathological sequelae and dea th in an otherwise resistant mouse strain provides an interesting focus for the burden of pathological attributes on death in an infectious disease.