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Titolo:
INTERLEUKIN-12 IS REQUIRED FOR THE T-LYMPHOCYTE-INDEPENDENT INDUCTIONOF INTERFERON-GAMMA BY AN INTRACELLULAR PARASITE AND INDUCES RESISTANCE IN T-CELL-DEFICIENT HOSTS
Autore:
GAZZINELLI RT; HIENY S; WYNN TA; WOLF S; SHER A;
Indirizzi:
NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB BETHESDA MD 20892 GENET INST INC CAMBRIDGE MA 02140
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 13, volume: 90, anno: 1993,
pagine: 6115 - 6119
SICI:
0027-8424(1993)90:13<6115:IIRFTT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; STIMULATORY FACTOR; TOXOPLASMA-GONDII; SCID MICE; CYTOKINE; ANTIBODY;
Keywords:
TOXOPLASMA-GONDII; NATURAL KILLER CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
R.T. Gazzinelli et al., "INTERLEUKIN-12 IS REQUIRED FOR THE T-LYMPHOCYTE-INDEPENDENT INDUCTIONOF INTERFERON-GAMMA BY AN INTRACELLULAR PARASITE AND INDUCES RESISTANCE IN T-CELL-DEFICIENT HOSTS", Proceedings of the National Academy of Sciences of the United Statesof America, 90(13), 1993, pp. 6115-6119

Abstract

Immunity against the intracellular protozoan Toxoplasma gondii is highly dependent on interferon gamma(IFN-gamma). We have previously shownthat, in addition to T lymphocytes, natural killer (NK) cells can be stimulated by the parasite to produce this cytokine by a reaction requiring adherent accessory cells and tumor necrosis factor alpha. We nowdemonstrate that a recently characterized cytokine, interleukin 12 (IL-12), is also necessary for parasite-induced IFN-gamma synthesis by NK cells. Anti-IL-12 antibodies completely inhibited T. gondii or bacterial endotoxin-stimulated IFN-gamma production by NK-enriched spleen cells from severe combined immunodeficient mice. Moreover, potent NK cytokine responses were induced by the combination of IL-12 and tumor necrosis factor alpha. In addition, adherent spleen cells from scid/scidmice or thyoglycollate-elicited macrophages from BALB/c animals produced high levels of both IL-12 (p40) and tumor necrosis factor alpha mRNAs when exposed to either live tachyzoites, parasite extracts, or endotoxin, confirming that these cytokines are produced by accessory cells. Finally, in vivo studies showed that treatment with recombinant IL-12 results in prolonged survival of scid mice after infection with T. gondii by means of a response dependent on both IFN-gamma and NK cells. Together the data argue that IL-12 is required for the T-cell-independent triggering of NK cells by intracellular parasites and that the cytokine may be useful for inducing this protective pathway in immunodeficient hosts.

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Documento generato il 28/11/20 alle ore 04:08:57