ADOPTIVE TRANSFER OF GUT INTRAEPITHELIAL LYMPHOCYTES PROTECTS AGAINSTMURINE INFECTION WITH TOXOPLASMA-GONDII

Intraepithelial lymphocytes (IEL) of the gut represent a primary immun e barrier against infection by orally acquired pathogens, Naturally ac quired infection with Toxoplasma gondii induces the proliferation of C D8(+) T cells in both the gut and spleen, Cut-derived CD8 alpha/beta() IEL exhibit MHC-restricted cytotoxicity against parasite-infected en terocytes and macrophages. In a murine model, we demonstrate that the adoptive transfer of IEL obtained from inbred mice at day 11 postinfec tion is able to protect against a virulent challenge in syngenic recip ients. In CBA mice, the parasite cyst load within the brain of the rec ipients receiving primed IEL was reduced by 90%. In BALB/c and C57BL/6 mice, a 50% decrease in mortality was observed following adoptive tra nsfer of primed IEL, To determine the T cell subset responsible fbr pr otective immunity, a purified CD8 alpha/beta(+) IEL population was iso lated from infected mice at day III postinfection, These cells were ab le to protect naive mice by adoptive transfer against a lethal parasit e challenge, RNA analysis by reverse-transcriptase PCR revealed that p rimed CD8 alpha/beta(+) IEL produce significant message for IFN-gamma, an essential cytokine for host protection against toxoplasmosis, Admi nistration of anti-IFN-gamma at the time of adoptive transfer of prime d 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 agai nst acute and perhaps recurrent infection with T. gondii.