CD40-ligand in primate cardiac allograft and viral immunity.

Pierson RN, Crowe JE, Pfeiffer S, Atkinson J, Azimzadeh A, Miller GG
Immunol Res. 2001 23 (2-3): 253-62

PMID: 11444390 · DOI:10.1385/IR:23:2-3:253

Our laboratory has studied the role of CD40 ligand (CD40L, CD154) in the primate immune response to allogenic and infectious challenges. We find that intensive early blockade of CD40L reliably attenuates acute rejection of primate cardiac allografts. Monotherapy fails to prevent late graft loss, which often occurs in association with rising antidonor antibody titers and allograft vasculopathy, despite continuing anti-CD40L therapy. In contrast, the primary humoral response to T helper dependent influenza viral antigen is inhibited during anti-CD40L therapy, and responses to subsequent immunization are blunted after discontinuation of therapy. These results are encouraging with regard to the tolerogenic potential of costimulatory blockade for specific T helper dependent antigens. However, these findings also indicate that pathogenic allograft responses in primates are probably not entirely CD40L-dependent. As such, additional immunomodulatory strategies are needed to facilitate tolerance to a transplanted organ.

MeSH Terms (28)

Abatacept Animals Antibodies, Monoclonal Antibodies, Viral Antibody Specificity Antigens, CD Antigens, Differentiation B-Lymphocytes CD40 Antigens CD40 Ligand CTLA-4 Antigen Graft Enhancement, Immunologic Graft Rejection Heart Transplantation Hemagglutinin Glycoproteins, Influenza Virus Humans Immune Tolerance Immunoconjugates Isoantibodies Macaca fascicularis Mice Skin Transplantation T-Lymphocytes, Helper-Inducer T-Lymphocyte Subsets Time Factors Transplantation, Heterotopic Transplantation, Homologous Vaccination

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