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Titolo:
Targeted delivery of anti-CTLA-4 antibody downregulates T cell function invitro and in vivo
Autore:
Rao, S; Vasu, C; Martinez, O; Kaithamana, S; Prabhakar, BS; Holterman, MJ;
Indirizzi:
Univ Illinois, Coll Med, Dept Surg, Div Pediat Surg, Chicago, IL 60612 USAUniv Illinois Chicago IL USA 60612 Div Pediat Surg, Chicago, IL 60612 USA Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 obiol & Immunol, Chicago, IL 60612 USA
Titolo Testata:
CLINICAL IMMUNOLOGY
fascicolo: 2, volume: 101, anno: 2001,
pagine: 136 - 145
SICI:
1521-6616(200111)101:2<136:TDOAAD>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYBRID ANTIBODY; CD28 COSTIMULATION; ALLOGRAFT SURVIVAL; CTLA-4; ACTIVATION; INDUCTION; MICE; TOLERANCE; BLOCKADE; DISEASE;
Keywords:
tolerance/suppression; costimulatory molecules; immunotherapy; antibodies;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Holterman, MJ Univ Illinois, Coll Med, Dept Surg, Div Pediat Surg, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 g, Chicago, IL 60612 USA
Citazione:
S. Rao et al., "Targeted delivery of anti-CTLA-4 antibody downregulates T cell function invitro and in vivo", CLIN IMMUNO, 101(2), 2001, pp. 136-145

Abstract

CTLA-4 is a T cell surface molecule that binds to the costimulatory molecules CD80 and CD86 on antigen-presenting cells and downregulates T cell function. Therefore, we wanted to test whether antigen-specific activated T cells could be inhibited through directed CTLA-4 signaling using a bispecific antibody (BiAb) capable of simultaneously binding to CTLA-4 and a tissue-specific antigen. The BiAb was prepared by linking two separate monoclonal antibodies against CTLA-4 and the thyroid-stimulating hormone receptor (TSHR). The mouse B cell lymphoma line M12 (H2(d)) was used to induce alloreactive T cells in CBA/J mice (H2(k)); M12 cells stably transfected with the cDNAencoding murine TSHR (mM12) were used to restimulate the alloresponse in vitro. Results of assays for in vitro T cell proliferation, IL-2 production,and cytoxicity in the presence of BiAb demonstrated that the BiAb could inhibit the T cell alloresponse when stimulated with mM12 cells but not with M12 cells. This effect was dependent on binding of TSHR-bound BiAb to CTLA-4, since the addition of soluble CTLA-4-Ig blocked the inhibitory effect. Injection of mM12 cells, along with the BiAb, not with antibodies against TSHR or CTLA-4 either separately or together, into CBA/J mice (H2(k)) downregulated alloreactive T cell responses. Our study demonstrated that the presence of CTLA-4 signaling molecules on the surface of target cells can protect those cells from immune attack by antigen-specific T cells and suggested that a similar approach could have potential therapeutic value in transplant rejection and tissue-specific autoimmune diseases. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 22:00:09