Protection of protozoa infection-physiological meaning of the activation of extrathymic T cells

点击翻译按钮获取中文摘要

In a series of recent studies, we as well as other investigators have characterized the nature of intermediate TCR (TCRィイD1intィエD1) cells in the liver of mice, in terms of the phenotype, morphology, and function. TCRィイD1intィエD1 cells are mainly present in the liver and are generated by an alternative intrathymic pathway (or possibly by the extrathymic pathway of T-cell differentiation in the liver. We examined in this study how these TCRィイD1intィエD1 cells, including NKT cells, are modulated during blood stage malarial infection. This object of the present study comes from the fact that malaria parasites are intracellular pathogens and that CD56ィイD1+ィエD1T and CD57ィイD1+ィエD1T cells (T cells which express NK cell markers) eventually expand in the peripheral blood of patients with malarial infection, including both Plasmodium (P.) falciparum and P. vivax (our unpublished observation).Mice were infected with Plasmodium (P.) yoelli, blood stage parasites. The major expanding cells were found to be TCRィイD1intィエD1 cells with the phenotype of NK1.1ィイD1-ィエD1 in the liver and other organs. NK1.1ィイD1-ィエD1 TCRィイD1intィエD1 cells which were purified from the liver in mice recovered from P. yoelli infection protected mice from malaria, when they were transferred into 6.5 Gy-irradiated mice. It was revealed that newly generated erythrocytes which still expressed class I MHC antigens in the bone marrow might be the targets for malarial infection. The present results suggest that TCRィイD1intィエD1 cells and other related subsets (e.g., a few NK1.1ィイD1+ィエD1TCRィイD1intィエD1 cells) are intimately associated with the protection from malarial infection.