ovalbumin and Parasitemia

Cerebral malaria is a potentially lethal disease, which is caused by excessive inflammatory responses to

Topics: Animals; Animals, Outbred Strains; Anopheles; Antigens, Protozoan; Brain; Cell Movement; Chemokine CCL5; Cytotoxicity, Immunologic; Eosinophils; Female; Leukocyte Count; Malaria, Cerebral; Mice; Mice, Inbred C57BL; Mice, Knockout; Mosquito Vectors; Organisms, Genetically Modified; Ovalbumin; Parasitemia; Peptide Fragments; Plasmodium berghei; Receptor, Interferon alpha-beta; Receptors, CCR5; Spleen; T-Lymphocytes

Cerebral malaria is one of the severe complications of Plasmodium falciparum infection. Studies using a rodent model of Plasmodium berghei ANKA infection established that CD8(+) T cells are involved in the pathogenesis of cerebral malaria. However, it is unclear whether and how Plasmodium-specific CD8(+) T cells can be activated during the erythrocyte stage of malaria infection. We generated recombinant Plasmodium berghei ANKA expressing OVA (OVA-PbA) to investigate the parasite-specific T cell responses during malaria infection. Using this model system, we demonstrate two types of CD8(+) T cell activations during the infection with malaria parasite. Ag (OVA)-specific CD8(+) T cells were activated by TAP-dependent cross-presentation during infection with OVA-PbA leading to their expression of an activation phenotype and granzyme B and the development to functional CTL. These highly activated CD8(+) T cells were preferentially sequestered in the brain, although it was unclear whether these cells were involved in the pathogenesis of cerebral malaria. Activation of OVA-specific CD8(+) T cells in RAG2 knockout TCR-transgenic mice during infection with OVA-PbA did not have a protective role but rather was pathogenic to the host as shown by their higher parasitemia and earlier death when compared with RAG2 knockout mice. The OVA-specific CD8(+) T cells, however, were also activated during infection with wild-type parasites in an Ag-nonspecific manner, although the levels of activation were much lower. This nonspecific activation occurred in a TAP-independent manner, appeared to require NK cells, and was not by itself pathogenic to the host.

Topics: Animals; CD8-Positive T-Lymphocytes; Cross-Priming; Interferon-gamma; Killer Cells, Natural; Lymphocyte Activation; Malaria; Malaria, Cerebral; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Parasitemia; Plasmodium berghei; Recombinant Fusion Proteins; T-Lymphocytes, Cytotoxic