IL-7 stimulates protective immunity in mice against the intracellular pathogen, Toxoplasma gondii.
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.
Kasper
L H
LH
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Matsuura
T
T
Khan
I A
IA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology; D015851:Interleukin-7 / Q000008:administration & dosage*; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy / Q000276:immunology*
D015851:Interleukin-7; D011994:Recombinant Proteins; D007371:Interferon-gamma