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Publication : IL-7 stimulates protective immunity in mice against the intracellular pathogen, Toxoplasma gondii.

First Author  Kasper LH Year  1995
Journal  J Immunol Volume  155
Issue  10 Pages  4798-804
PubMed ID  7594482 Mgi Jnum  J:29631
Mgi Id  MGI:77156 Doi  10.4049/jimmunol.155.10.4798
Citation  Kasper LH, et al. (1995) IL-7 stimulates protective immunity in mice against the intracellular pathogen, Toxoplasma gondii. J Immunol 155(10):4798-804
abstractText  Cytokines, in particular IFN-gamma and IL-12, are important in host protection against infection with Toxoplasma gondii. This parasite is a major cause of congenital infection and morbidity in immunosuppressed persons, especially those with AIDS. IL-7, a monomeric protein produced by bone marrow stromal cells and fetal thymus, is able to induce the proliferation of pro-B cells and CD4+ and CD8+ T cells, and to enhance cytotoxicity of CTL and NK cells. Inbred mice were infected with a lethal dose of T. gondii and given IL-7 twice daily. Mice treated with IL-7 beginning at the time of infection survived, whereas mice either treated after infection or not treated died. Phenotypic analysis of splenocytes identified an expansion of NK (asialo GM1+) cells and CD8+ T cell populations. In vivo depletion of NK (asialo GM1+) and CD8+ T cells showed that cells expressing these phenotypes were important for maintaining protection against the parasite. IFN-gamma depletion resulted in complete reversal of the protective effect of IL-7 administration. In vivo depletion of endogenous IL-7 enhanced susceptibility to infection. Cytokine analysis by semiquantitative reverse-transcriptase PCR showed that IL-7 enhances the IFN-gamma response and furthermore reverses the parasite-mediated down-regulatory response on IL-2. These observations indicate that exogenous administration of human rIL-7 is able to protect mice against acute parasite challenge by stimulating IFN-gamma production and augmenting the CD8+ T cell-mediated CTL response.
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