Inhibition of Transplant Rejection Following Treatment With Anti-B7-2 and Anti-B7-1 Antibodies

Lenschow, Deborah J.; Zeng, Yijun; Hathcock, K. S.; Zuckerman, L; Freeman, Gordon J.; Thistlethwaite, J. Richard; Gray, Gary S.; Hodes, Richard J.; Bluestone, J. A.

doi:10.1097/00007890-199511270-00019

Cited by 150 publications

(84 citation statements)

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“…Previous studies have shown that CD28/B7 blockade significantly inhibited allogeneic proliferative responses in vitro (23,32,57). Moreover, combined CD28/B7 and CD154/ CD40 blockade had the most profound inhibitory effect on…”

Section: Co-stimulatory Blockade Inhibits Direct Antigen Presentationmentioning

confidence: 87%

“…Numerous studies also indicated that the CD28/B7 and CD154/CD40 costimulatory pathways were critical regulators of allograft rejection (24,25,(27)(28)(29)(30)(31)(32)(33)(34)(35), Direct Class II Antigen Presentation and Tolerance specifically in CD4π T-cell-mediated rejection (36,37). Recent studies point to a differential role of CD28/B7 and CD154/CD40 costimulation in CD4 vs. CD8 T-cell-mediated allogeneic responses.…”

Section: Introductionmentioning

confidence: 99%

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Inability to Induce Tolerance Through Direct Antigen Presentation

Rulifson

Szot

Palmer

et al. 2002

American Journal of Transplantation

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Both the direct and indirect antigen presentation pathways are important mechanisms for T cell-mediated allograft rejection. Studies using knockout mice and monoclonal antibodies have demonstrated that CD4π T cells are both necessary and sufficient for the rejection of allogeneic tissues, including skin, heart, and islet. Furthermore, combined blockade of the CD28/B7 and CD154/CD40 costimulatory pathways induces tolerance in multiple CD4π T-cell dependent allograft models. In this study, we addressed the T-cell requirement for costimulation in direct antigen presentation. We demonstrated that class II-specific alloreactive Tcell receptor transgenic T cells were sufficient to mediate allograft rejection independent of costimulatory blockade. Analysis of the costimulatory capacity of different antigen presenting cell (APC) populations demonstrated that APCs resident within the donor skin, Langerhans cells, are potent stimulators not requiring CD28-or CD154-dependent costimulation for direct major histocompatibility complex (MHC) antigen presentation. These results complement previous work examining the role of costimulation on CD8π T cells, supporting a model in which the effectiveness of costimulatory blockade in the setting of transplantation may be selective for the indirect pathway of MHC alloantigen presentation.

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Section: Co-stimulatory Blockade Inhibits Direct Antigen Presentationmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Inability to Induce Tolerance Through Direct Antigen Presentation

Rulifson

Szot

Palmer

et al. 2002

American Journal of Transplantation

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“…20 Indeed, blockade of the interaction of CD28 with B7 will prevent experimental transplant rejection, presumably because alloreactive T cells undergo apoptosis without the costimulatory signal. 21,22 The mechanisms by which costimulation protects from apoptosis may involve augmented lymphokine (e.g., IL-2) production that acts as a cell survival stimulus. In addition, CD28 also enhances Bcl-X L production, thereby conferring greater resistance against apoptosis.…”

Section: Role Of Apoptosis In Controlling T-cell Responses After Actimentioning

confidence: 99%

Apoptosis in liver transplantation: A mechanism contributing to immune modulation, preservation injury, neoplasia, and viral disease

Patel

Gores

1998

Liver Transpl

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“…106,[109][110][111][112] In a set of experiments where murine islet allografts were coated with CTLA-4Ig, transplantation led to prolongation of graft survival to more than 150 days in 50% of the hosts which also exhibited donorspecific tolerance despite the presence of a noninvasive CD4 + and CD8 + T lymphocyte peri-islet accumulation. 113 The importance of the B7-CD28 pathway in allograft acceptance was further demonstrated by Lenschow et al 114 who used Abs against CD80 and CD86, alone or in combination to prolong murine allogeneic islet survival. Interestingly, the effects of the anti-CD86 antibody on allograft survival were more pronounced than those of the anti-CD80 antibody.…”

Section: Inhibition Of Costimulationmentioning

confidence: 98%

“…Interestingly, the effects of the anti-CD86 antibody on allograft survival were more pronounced than those of the anti-CD80 antibody. 114 Recently, CTLA-4Ig has been used to prolong pancreatic islet allograft survival in a monkey model, where in addition to prolongation of allograft survival, donor-specific hyporesponsiveness was observed in vitro, as well as suppression of humoral responses. 115 More recently, transfer of CTLA-4Ig cDNA to allogeneic as well as xenogeneic tissues destined for transplantation, has yielded encouraging results.…”

Section: Inhibition Of Costimulationmentioning

confidence: 99%