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Titolo:
RECOMBINANT T-CELL RECEPTOR MOLECULES CAN PREVENT AND REVERSE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - DOSE EFFECTS AND INVOLVEMENT OF BOTH CD4 AND CD8 T-CELLS
Autore:
KUMAR V; COULSELL E; OBER B; HUBBARD G; SERCARZ E; WARD ES;
Indirizzi:
LA JOLLA INST ALLERGY & IMMUNOL,DIV IMMUNE REGULAT,10355 SCI CTR DR SAN DIEGO CA 92121 UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOL GENET LOS ANGELES CA 90095 UNIV TEXAS,SW MED CTR,DEPT MICROBIOL DALLAS TX 75235 UNIV TEXAS,SW MED CTR,CTR CANC IMMUNOBIOL DALLAS TX 75235
Titolo Testata:
The Journal of immunology
fascicolo: 10, volume: 159, anno: 1997,
pagine: 5150 - 5156
SICI:
0022-1767(1997)159:10<5150:RTRMCP>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; MULTIPLE-SCLEROSIS; GENE REARRANGEMENTS; ANTIGEN RECOGNITION; CLONAL EXPANSION; PEPTIDE ANALOG; V-ALPHA; DETERMINANTS;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
V. Kumar et al., "RECOMBINANT T-CELL RECEPTOR MOLECULES CAN PREVENT AND REVERSE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - DOSE EFFECTS AND INVOLVEMENT OF BOTH CD4 AND CD8 T-CELLS", The Journal of immunology, 159(10), 1997, pp. 5150-5156

Abstract

Autoimmune diseases are often characterized by spontaneous remission followed by relapses, Although the mechanism(s) controlling pathogenicself-reactive T cells are not fully understood, recent data in experimental autoimmune encephalomyelitis (EAE), a prototype for CD4 T cell-mediated autoimmune diseases, indicate that spontaneous recovery is mediated by regulatory T cells (Treg) specific for peptides derived fromthe beta-chain of the TCR, Here we have tested whether recombinant single-chain TCRs (scTCRs) containing V beta domains can be used as vaccines for efficient priming of Treg, A single injection of mice with these recombinant proteins leads to efficient in vivo priming of Treg and almost complete protection from Ag-induced EAE, Significantly, administration of scTCRs during ongoing disease at a 10-fold lower dose than that required for prophylactic treatment also reverses established EAE. However, if a higher dose of scTCR is administered during ongoing disease, paralytic symptoms become exacerbated and the majority of treated animals die from severe and chronic EAE, Furthermore, we demonstrate that regulatory determinants are processed and presented from scTCRs resulting in the recruitment of both CD4 and CD8 regulatory T cellswhich are required for efficient regulation induced by scTCR, Reversal of established disease following an optimum dose of recombinant TCRssuggests that proteins expressing appropriate V beta domains could beused for the treatment of a variety of T cell-mediated pathologic conditions.

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Documento generato il 25/11/20 alle ore 10:10:03