Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models.

Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Research Abstract Details 

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Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Abstract Text:

M L Ford,M E Wagener,S Gangappa,T C Pearson,C P Larsen,

Treatment regimens consisting of CTLA-4 Ig/anti-CD154 or agonistic anti-CD28/rapamycin have both been shown to prevent GVHD in fully allogeneic murine model systems. Using a transgenic approach to track the fate of host-reactive T cells in a minor antigen disparity model of GVHD, we found that while treatment with CTLA-4 Ig/anti-CD154 retained efficacy, the costimulation agonist anti-CD28 combined with rapamycin failed to prevent GVHD. Analysis of the host-reactive CD4(+) and CD8(+) T-cell responses revealed that in contrast to CTLA-4Ig/anti-CD154-treated recipients, host-reactive T cells in recipients treated with agonistic anti-CD28/rapamycin displayed enhanced and accelerated T-cell proliferation and failed to undergo activation-induced cell death. An increase in systemic levels of inflammatory cytokines was observed in the anti-CD28/rapamycin-treated recipients of the minor but not major antigen disparity bone marrow transplants. Our results demonstrate the intricacies of costimulatory receptor signaling pathways, and reveal how agonism of the CD28 pathway can have opposing outcomes depending on the degree of antigenic disparity.

Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Publishing Authors By Initials

ML Ford,ME Wagener,S Gangappa,TC Pearson,CP Larsen,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of transplantation : official jou

VOLUME: 7

Page Numbers: 1471-81

Journal Abbreviation: Am. J. Transplant.

ISSN: 1600-6135

DAY: 3

MONTH: Jun

YEAR: 2007

Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Information

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LANGUAGE: eng

NlmUniqueID: 100968638

Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: immunology

Chemical & Substance for Abstract: Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models. Information

Substance Name: Sirolimus

Registry Number: 53123-88-9

Grant and Affiliation Information for Antigenic disparity impacts outcome of agonism but not blockade of costimulatory pathways in experimental transplant models.

AFFILIATION: Department of Surgery, Emory Transplant Center, Emory University, Atlanta, GA, USA.

Country: Denmark

AGENCY: United States NIAID

GRANT: AI040519

ACRONYM: AI

MEDLINETA: Am J Transplant

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