Inhibition of transplant rejection following treatment with anti-B7-2 and anti-B7-1 antibodies.
Transplantation
; 60(10): 1171-8, 1995 Nov 27.
Article
em En
| MEDLINE
| ID: mdl-7482727
ABSTRACT
Antigen-specific T cell activation depends initially on the interaction of the T cell receptor (TCR) with peptide/MHC. In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules, is required for complete T cell activation leading to lymphokine production and proliferation. CD28 has been implicated as the major receptor on T cells responsible for delivering the costimulatory signal. Although two distinct ligands for CD28, B7-1 and B7-2, have been identified on antigen-presenting cells (APC), the co-stimulatory role of each molecule during a physiological immune response remains unresolved. In the present study, the relative roles of B7-1 and B7-2 interactions were evaluated in an allogeneic pancreatic islet transplant setting. In isolation, anti-B7-2 mAbs and, to a much lesser degree, anti-B7-1 mAbs suppressed T cell proliferative responses to allogeneic islets or splenic APC in vitro. Maximal inhibition of the allogeneic response was observed using a combination of the anti-B7-1 and anti-B7-2 mAbs. Administration of anti-B7-2 but not anti-B7-1 mAbs prolonged C3H allograft survival in B6 recipients, with a combination of both mAbs significantly prolonging rejection beyond either mAb alone. The immunosuppressive effects of the in vivo mAb treatment were not manifested in in vitro analyses as T cells isolated from suppressed mice responded normally to allogeneic stimuli in terms of both proliferation and lymphokine production. However, combined mAb therapy in vivo selectively delayed CD4+ T lymphocyte infiltration into the graft. These data suggest that both B7-1 and B7-2 costimulatory molecules are active in vivo, although B7-2 plays a clearly dominant role in this allograft model. The mechanism of immune suppression in vivo remains unresolved but may occur at sites distinct from the allograft.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Antígenos CD
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Transplante das Ilhotas Pancreáticas
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Antígeno B7-1
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Imunoconjugados
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Rejeição de Enxerto
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Anticorpos Monoclonais
Limite:
Animals
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article