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Titolo:
IN-VIVO MICROBIAL STIMULATION INDUCES RAPID CD40 LIGAND-INDEPENDENT PRODUCTION OF INTERLEUKIN-12 BY DENDRITIC CELLS AND THEIR REDISTRIBUTION TO T-CELL AREAS
Autore:
SOUSA CRE; HIENY S; SCHARTONKERSTEN T; JANKOVIC D; CHAREST H; GERMAIN RN; SHER A;
Indirizzi:
NIAID,LBS,LI,DIR,NIH,BLDG 10,RM 11N311,10 CTR DR,MSC 1892 BETHESDA MD20892 NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH BETHESDA MD 20892
Titolo Testata:
The Journal of experimental medicine
fascicolo: 11, volume: 186, anno: 1997,
pagine: 1819 - 1829
SICI:
0022-1007(1997)186:11<1819:IMSIRC>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; IFN-GAMMA; TOXOPLASMA-GONDII; PHENOTYPE DEVELOPMENT; MONOCLONAL-ANTIBODY; LANGERHANS CELLS; IL-12 PRODUCTION; ACUTE INFECTION; UP-REGULATION;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
C.R.E. Sousa et al., "IN-VIVO MICROBIAL STIMULATION INDUCES RAPID CD40 LIGAND-INDEPENDENT PRODUCTION OF INTERLEUKIN-12 BY DENDRITIC CELLS AND THEIR REDISTRIBUTION TO T-CELL AREAS", The Journal of experimental medicine, 186(11), 1997, pp. 1819-1829

Abstract

The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (M Phi) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4(+) lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not M Phi are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. importantly, this production of IL-12 occurs very rapidly and is independent of interferon gamma priming or of signals from T cells, such as CD40ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendriticcells. The capacity of splenic DC but not M Phi to synthesize de novohigh levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migrationof DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 23:47:51