OX40 (CD134) blockade inhibits the co-stimulatory cascade and promotes heart allograft survival
Abstract
CD134 (OX40) is a member of the tumor necrosis factor receptor superfamily that is expressed as a late event in T-cell activation and contributes to the generation of immunologic memory. CD134 blockade effectively ameliorates inflammation in models of autoimmune disease, but its role in transplantation has been less well studied. The authors used an OX40-immunoglobulin (Ig) fusion protein to examine the contribution of this co-stimulatory molecule to the in vitro alloimmune response and studied the ability of CD134 blockade to prevent cardiac allograft rejection in mouse models of heart transplantation using strains representing both major histocompatibility complex (MHC) (BALB/c to CBA/Ca) and minor histocompatibility complex (mHC) (B10.BR to CBA/Ca) antigen mismatches. CD134 upregulation on in vitro alloactivated T cells was delayed compared with CD69 and CD25, and inhibition of T-cell proliferation was critically dependent on the timing of OX40-Ig administration. Heart allograft survival in a fully allogeneic, MHC-mismatched strain combination was not influenced by CD134 blockade alone, but OX40-Ig treatment in the mHC-mismatched model resulted in long-term graft survival (median survival time extended from 14 days to >100 d...Continue Reading
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