Adoptive transfer of gut intraepithelial lymphocytes protects against murine infection with Toxoplasma gondii.
Intraepithelial lymphocytes (IEL) of the gut represent a primary immune barrier against infection by orally acquired pathogens. Naturally acquired infection with Toxoplasma gondii induces the proliferation of CD8+ T cells in both the gut and spleen. Gut-derived CD8alpha/beta+ IEL exhibit MHC-restricted cytotoxicity against parasite-infected enterocytes and macrophages. In a murine model, we demonstrate that the adoptive transfer of IEL obtained from inbred mice at day 11 postinfection is able to protect against a virulent challenge in syngenic recipients. In CBA mice, the parasite cyst load within the brain of the recipients receiving primed IEL was reduced by 90%. In BALB/c and C57BL/6 mice, a 50% decrease in mortality was observed following adoptive transfer of primed IEL. To determine the T cell subset responsible for protective immunity, a purified CD8alpha/beta+ IEL population was isolated from infected mice at day 11 postinfection. These cells were able to protect naive mice by adoptive transfer against a lethal parasite challenge. RNA analysis by reverse-transcriptase PCR revealed that primed CD8alpha/beta+ IEL produce significant message for IFN-gamma, an essential cytokine for host protection against toxoplasmosis. Administration of anti-IFN-gamma at the time of adoptive transfer of primed IEL abrogated protection. The adoptive transfer of these protective IEL was not restricted to the Ld class I locus. These data demonstrate that IFN-gamma-producing IEL may be an important primary barrier against acute and perhaps recurrent infection with T. gondii.
Buzoni-Gatel
D
D
Immunology of Infectious Diseases (CJF INSERM 93-09), Equipe associée INRA (Institut National de la Recherche Agronomique) d'Immunologie Parasitaire, Tours, France. buzoni@balzac.univ-tours.fr
Lepage
A C
AC
Dimier-Poisson
I H
IH
Bout
D T
DT
Kasper
L H
LH
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004848:Epithelium / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D007371:Interferon-gamma