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Titolo:
SPECIFIC DOWN-REGULATION OF PROLIFERATIVE T-CELL ALLORESPONSIVENESS BY INTERFERENCE WITH CD2 LFA-3 AND LFA-1/ICAM-1 IN-VITRO/
Autore:
BOHMIG GA; KOVARIK J; HOLTER W; POHANKA E; ZLABINGER GJ;
Indirizzi:
UNIV VIENNA,INST IMMUNOL,BORSCHKEGASSE 8A A-1090 VIENNA AUSTRIA UNIV VIENNA,INST IMMUNOL A-1090 VIENNA AUSTRIA UNIV VIENNA,DEPT INTERNAL MED 3 VIENNA AUSTRIA UNIV VIENNA,VIRCC,INST IMMUNOL VIENNA AUSTRIA
Titolo Testata:
The Journal of immunology
fascicolo: 8, volume: 152, anno: 1994,
pagine: 3720 - 3728
SICI:
0022-1767(1994)152:8<3720:SDOPTA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLASS-II MHC; TRANSGENIC MICE; ANTIGEN-PRESENTATION; LYMPHOCYTES-T; CLONAL ANERGY; MOLECULES; INDUCTION; ACTIVATION; TOLERANCE; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
G.A. Bohmig et al., "SPECIFIC DOWN-REGULATION OF PROLIFERATIVE T-CELL ALLORESPONSIVENESS BY INTERFERENCE WITH CD2 LFA-3 AND LFA-1/ICAM-1 IN-VITRO/", The Journal of immunology, 152(8), 1994, pp. 3720-3728

Abstract

T cell activation requires Ag contact with the TCR in the presence ofcostimulatory signals provided by APCs. When Ag is presented without costimulation, T cells are functionally inactivated. Here we demonstrate that interference with distinct adhesion molecules during Ag contact using mAbs leads to Ag-specific functional inactivation of alloreactive T cells. We found that the presence of a mixture of mAbs specific for CD2, LFA-3, LFA-1 alpha- and beta-chain, and ICAM-1 during primaryMLC leads to down-regulation of secondary proliferative responses to Ag from the donor used for priming. Cells from pretreated cultures proliferated well, however, when stimulated with Ag from third party donors, mitogens, or mitogenic CD3 mAb. Because specific reactivity could be restored by addition of IL-2 to restimulation cultures, altered secondary responsiveness appeared to be caused by anergy and not by elimination of specific clones. Furthermore, specific down-regulation of alloresponsiveness was prevented by addition of IL-2 to primary culturesin the presence of mAb. Interference by mAb with either CD2/LFA-3, LFA-1/ICAM-1, CD2/LFA-1, or LFA-3/ICAM-1 had a substantial, though less pronounced effect on secondary responsiveness. After pretreatment withthe Ab mixture, CTL generation was substantially but incompletely downregulated against the original and third party donors. Because a decrease in the reactivity of unstimulated responders by culture was also observed, these findings might be explained by the loss of cytotoxic precursors after culturing under nonstimulating conditions. In conclusion, our data demonstrate that T cells enter a state of anergy when T cell activation is modulated by simultaneous interference with distinctadhesion molecules during Ag contact, which thus might reflect at least partly overlapping functions of particular receptor-ligand pairs inT cell costimulation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 03:37:46