The CD154-CD40 costimulatory pathway in transplantation.

Abstract:

:The CD154-CD40 pathway is one of the critical costimulatory pathways that are required for full activation of T cells during alloimmune responses. Blockade of this pathway with anti-CD154 antibodies has been reported to prolong allograft survival in experimental transplantation models and to induce tolerance in some instances. However, anti-CD154 monotherapy cannot induce tolerance in "stringent" models such as skin and islet transplantation and is not sufficient to prevent chronic graft vasculopathy in vascularized organ transplantation. Therefore, combined therapies of anti-CD154 antibodies plus donor-specific transfusion, bone marrow infusion, or B7 blockade by CTLA4-Ig have been tried, and synergistic effects for tolerance induction have been reported. Furthermore, the efficacy of CD154 blockade in primate models has been confirmed for islet and kidney transplantation. The mechanisms of CD154 blockade in vivo include CTLA4-dependent anergy or regulation, T-cell apoptosis, and induction of regulatory cells. Finally, anti-CD154 antibody therapy has been reported to result in unexpected thromboembolic complications in both primates and humans, although the etiology of these conditions remains unclear. In addition, not all antibodies cause this side effect. Clinical trials with humanized anti-CD154 monoclonal antibodies are underway in severe autoimmune diseases, but its development in transplantation is unclear at this time.

journal_name

Transplantation

journal_title

Transplantation

authors

Yamada And A,Sayegh MH

doi

10.1097/00007890-200201151-00012

subject

Has Abstract

pub_date

2002-01-15 00:00:00

pages

S36-9

issue

1 Suppl

eissn

0041-1337

issn

1534-6080

journal_volume

73

pub_type

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