Targeted delivery of anti-CTLA-4 antibody downregulates T cell function in vitro and in vivo

Copyright 2001 Academic Press.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 101(2001), 2 vom: 01. Nov., Seite 136-45
1. Verfasser: Rao, S (VerfasserIn)
Weitere Verfasser: Vasu, C, Martinez, O, Kaithamana, S, Prabhakar, B S, Holterman, M J
Format: Aufsatz
Sprache:English
Veröffentlicht: 2001
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Antibodies, Bispecific Antibodies, Monoclonal Antigens, CD Antigens, Differentiation CTLA-4 Antigen Ctla4 protein, mouse Immunoconjugates mehr... Immunosuppressive Agents Interleukin-2 Receptors, Thyrotropin Abatacept 7D0YB67S97
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245 1 0 |a Targeted delivery of anti-CTLA-4 antibody downregulates T cell function in vitro and in vivo 
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520 |a 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 cDNA encoding murine TSHR (mM12) were used to restimulate the alloresponse in vitro. Results of assays for in vitro T cell proliferation, IL-2 production, and cytotoxicity 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, P.H.S. 
650 7 |a Antibodies, Bispecific  |2 NLM 
650 7 |a Antibodies, Monoclonal  |2 NLM 
650 7 |a Antigens, CD  |2 NLM 
650 7 |a Antigens, Differentiation  |2 NLM 
650 7 |a CTLA-4 Antigen  |2 NLM 
650 7 |a Ctla4 protein, mouse  |2 NLM 
650 7 |a Immunoconjugates  |2 NLM 
650 7 |a Immunosuppressive Agents  |2 NLM 
650 7 |a Interleukin-2  |2 NLM 
650 7 |a Receptors, Thyrotropin  |2 NLM 
650 7 |a Abatacept  |2 NLM 
650 7 |a 7D0YB67S97  |2 NLM 
700 1 |a Vasu, C  |e verfasserin  |4 aut 
700 1 |a Martinez, O  |e verfasserin  |4 aut 
700 1 |a Kaithamana, S  |e verfasserin  |4 aut 
700 1 |a Prabhakar, B S  |e verfasserin  |4 aut 
700 1 |a Holterman, M J  |e verfasserin  |4 aut 
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