Prolonged survival in rat liver transplantation with mouse monoclonal antibody against an inducible costimulator (ICOS) 1
L Guo, XK Li, N Funeshima, M Fujino, Y Nagata… - …, 2002 - journals.lww.com
L Guo, XK Li, N Funeshima, M Fujino, Y Nagata, H Kimura, H Amemiya, S Enosawa, T Tsuji…
Transplantation, 2002•journals.lww.comBackground. An inducible costimulator (ICOS), a recently identified costimulatory receptor
with a close structural homology to CD28 and CTLA4, is expressed on activated T cells.
Interaction with its ligand on antigen-presenting cells stimulates T-cell proliferation to
produce a different spectrum of cytokine. The inhibition of ICOS-mediated signal
transduction by an anti-ICOS antibody is considered to be capable of protecting against graft
rejection in organ transplantation. Methods. An anti-rat ICOS antibody was intravenously …
with a close structural homology to CD28 and CTLA4, is expressed on activated T cells.
Interaction with its ligand on antigen-presenting cells stimulates T-cell proliferation to
produce a different spectrum of cytokine. The inhibition of ICOS-mediated signal
transduction by an anti-ICOS antibody is considered to be capable of protecting against graft
rejection in organ transplantation. Methods. An anti-rat ICOS antibody was intravenously …
Abstract
Background.
An inducible costimulator (ICOS), a recently identified costimulatory receptor with a close structural homology to CD28 and CTLA4, is expressed on activated T cells. Interaction with its ligand on antigen-presenting cells stimulates T-cell proliferation to produce a different spectrum of cytokine. The inhibition of ICOS-mediated signal transduction by an anti-ICOS antibody is considered to be capable of protecting against graft rejection in organ transplantation.
Methods.
An anti-rat ICOS antibody was intravenously administered into recipients of dark Agouti-to-Lewis liver transplantations. The recipient lymphocytes from mesenteric lymph nodes were harvested on day 7 after transplantation for fluorescence-activated cell sorting analysis, and tissue specimens from the grafts were removed for histologic evaluation. Antigen-specific T-cell proliferation responses were assessed in vitro with anti-ICOS antibody.
Results.
Monotherapy with the antibody significantly prolonged the graft survival time by inhibiting T-cell activation and its proliferation response. The graft-infiltrating cells, both CD4 and CD8 T cells, were not completely reduced even when rats were administered the antibody, whereas the expression of ICOS almost completely disappeared in these cells.
Conclusions.
T-cell activation through the ICOS costimulatory pathway plays an important role in graft rejection, and manipulating its pathway is an effective method for modulating transplantation immunity.
Lippincott Williams & Wilkins