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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).