Circulation, Ahead of Print. BACKGROUND:The entrance of naive T cells into lymph nodes (LNs) is a crucial step for induction of heart transplant acceptance under costimulatory blockade.
Specialized blood vessels within the LN known as high endothelial venules (HEVs) mediate this process. HEVs express a key glycoprotein containing 6-sulfo sialyl Lewis X, the binding site for L-selectin on the membrane of naive T cells.
The proper formation of this carbohydrate requires sulfation by N-acetylglucosamine 6-O-sulfotransferases, particularly CHST4. Given the critical role of CHST4 in HEVs and transplant immunity, we aimed to develop a first-in-class antibody-drug conjugate (ADC) targeting the CHST4/HEV axis to deliver immunoregulatory molecules to LNs and promote long-term cardiac transplant survival.METHODS:We used CHST4 knockout mice and inducible diphtheria toxin receptor mouse models to investigate the role of CHST4 in HEV function during heart allograft transplantation.
To assess the impact of CHST4 deficiency on heart transplant outcomes, we used fully major histocompatibility complex–mismatched and single major histocompatibility complex class II–mismatched models to study acute and chronic heart transplant rejection, respectively.
Circulation published a clinical update in Cardiology on 20 Feb 2026.
The item focuses on HEV-Targeted Antibody-Drug Conjugate Promotes Long-Term Cardiac Allograft Acceptance.
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