       Document 0531
 DOCN  M9620531
 TI    IL-7 stimulates protective immunity in mice against the intracellular
       pathogen, Toxoplasma gondii.
 DT    9602
 AU    Kasper LH; Matsuura T; Khan IA; Department of Medicine, Dartmouth
       Medical School, Hanover, NH; 03755, USA.
 SO    J Immunol. 1995 Nov 15;155(10):4798-804. Unique Identifier : AIDSLINE
       MED/96062298
 AB    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.
 DE    Animal  CD8-Positive T-Lymphocytes/*IMMUNOLOGY  Female  Human
       *Immunity, Cellular/DRUG EFFECTS  Interferon Type II/IMMUNOLOGY
       Interleukin-7/*ADMINISTRATION & DOSAGE  Mice  Recombinant
       Proteins/ADMINISTRATION & DOSAGE  Spleen/IMMUNOLOGY  Support, U.S.
       Gov't, P.H.S.  Toxoplasma/*IMMUNOLOGY  Toxoplasmosis, Animal/DRUG
       THERAPY/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

