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Titolo:
The identification of a novel T cell activation state controlled by a diabetogenic gene
Autore:
Moore, JK; Scheinman, RI; Bellgrau, D;
Indirizzi:
Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Sch Med,Dept Immunol, Denver, CO 80262 USA Univ Colorado Denver CO USA 80262 Med,Dept Immunol, Denver, CO 80262 USA Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80262 USA Univ Colorado Denver CO USA 80262 pt Pharmaceut Sci, Denver, CO 80262 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 1, volume: 166, anno: 2001,
pagine: 241 - 248
SICI:
0022-1767(20010101)166:1<241:TIOANT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIN-DEPENDENT KINASES; RECENT THYMIC EMIGRANTS; LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; BB RAT; NUCLEAR ANTIGEN; P27(KIP1) EXPRESSION; NEGATIVE SELECTION; INHIBITOR P27; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Bellgrau, D Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Sch Med,Dept Immunol, B 4200 E 9th Ave, Denver, CO 80262 USA Univ Colorado B 4200 E 9th Ave Denver CO USA 80262 O 80262 USA
Citazione:
J.K. Moore et al., "The identification of a novel T cell activation state controlled by a diabetogenic gene", J IMMUNOL, 166(1), 2001, pp. 241-248

Abstract

The cyclin-dependent kinase inhibitor p27(kip) regulates the cell cycle atthe G(1)-S phase restriction point. S phase entry and cell cycle commitment in peripheral T cells requires p27(kip) degradation, normally initiated by the receipt of costimulatory signals such as those provided by B7.1 or IL-2. We have previously reported that T cells from BioBreeding (BB)-diabetes-prone (DP) rats exhibit decreased costimulatory requirements for activation and cell cycle entry. In the present study, we find that peripheral T cell subsets from BB-DP rats demonstrate activation-like characteristics, including significantly reduced levels of p27(kip) as well as increased levels of proliferating cell nuclear Ag (PCNA), Since our previous studies have established that expression of extracellular activation markers are relatively low in unmanipulated peripheral BB-DP T cells; this p27(low) PCNA(high) phenotype represents a novel activation state, Analyses of T cell subsets from congenic rats demonstrate that this phenotype segregates with the lyp diabetogenic locus and that the p27(low) pCNA(high) phenotype is T cell specific. This p27(low) PCNA(high) phenotype is not seen in medullary thymocytes, but appears abruptly in the recent thymic emigrant population, suggestingthat the lyp locus does not act directly on cell cycle regulators but rather alters the interaction between T cells and the peripheral environment, These results provide a biochemical basis for costimulation-independent activation and suggest a mechanism whereby a diabetes susceptibility gene contributes to disease development.

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Documento generato il 30/11/20 alle ore 07:18:04