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CTLA-41g in combination with anti-CD40L prolongs xenograft survival and inhibits anti-gal ab production in GT-Ko mice

Yin, D; Ma, L; Shen, J; Byrne, GW; Logan, JS; Chong, AS; (2002) CTLA-41g in combination with anti-CD40L prolongs xenograft survival and inhibits anti-gal ab production in GT-Ko mice. Am J Transplant , 2 (1) 41 - 47.

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Abstract

The generation of GT-Ko mice has provided unique opportunities to study allograft and xenograft rejection in the context of anti-alpha1,3-Gal antibody (anti-Gal Ab) responses. In this study we used the allotransplantation model of C3H hearts into galactosyltransferase-deficient (GT-Ko) mice and the xenotransplantation model of baby Lewis rat hearts into GT-Ko mice to investigate the ability of CTLA-41g in combination with anti-CD40L mAb to control graft rejection and anti-Gal Ab production. Murine CTLA-41g or anti-CD40L monotherapy prolonged allograft survival, and the combination of these reagents was most immunosuppressive. However short-term treatment with murine cytotoxic T lymphocyte associated antigen-4 (muCTLA-41g) and/or CD40 ligand (CD154) monoclonal antibodies (anti-CD40L mAbs) was unable to induce indefinite allograft survival. CTLA-4-immunoglobulin fusion protein (CTLA-41g) or anti-CD40L monotherapy only marginally prolonged xenograft survival; the combination of human CTLA-41g and anti-CD40L significantly prolonged xenograft survival (74days), while the combination of murine CTLA-41g and anti-CD40L resulted in graft survival of >120days. CTLA-41g or anti-CD40L monotherapy or the combination of these agents inhibited the production of alloAbs, including anti-Gal Abs. CTLA-41g or anti-CD40L monotherapy partially controlled xenoAb and anti-Gal Ab production, while the combination was more effective. These observations corroborate our previous observations that humoral, including anti-Gal Ab, responses and rejection following allograft or concordant xenograft transplantation in GT-Ko mice are T-cell dependent and can be controlled by costimulation blockade.

Type:Article
Title:CTLA-41g in combination with anti-CD40L prolongs xenograft survival and inhibits anti-gal ab production in GT-Ko mice
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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