Major Histocompatibility Complex Class I Matching is Necessary but not Sufficient for Tolerance Induction to Vascularized Composite Allografts After Donor Hematopoietic Cell Transplantation
Transplantation Direct, cilt.12, sa.2, 2026 (ESCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 12 Sayı: 2
- Basım Tarihi: 2026
- Doi Numarası: 10.1097/txd.0000000000001900
- Dergi Adı: Transplantation Direct
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, MEDLINE, Directory of Open Access Journals
- Hacettepe Üniversitesi Adresli: Evet
Özet
Background. – We previously reported a porcine model of vascularized composite allograft (VCA) transplantation with concurrent hematopoietic cell transplantation (HCT). Tolerance developed when major histocompatibility complex (MHC) class I was matched in the absence of class II matching but not when class II was matched without class I matching. We investigated whether rejection resulted from a mismatch between class I and class II. Methods. – Recipient pigs were either mismatched from donors by a single class I haplotype or matched by a single class II haplotype. They received CD3 immunotoxin and total-body irradiation followed by HCT and VCA transplantation from the same donor. Cyclosporine immunosuppression was discontinued after 45 d. Results. – Pigs mismatched for only 1 MHC class I haplotype maintained peripheral chimerism and accepted the VCA graft, except for 1 animal that rejected the epidermis. Pigs matched for only 1 MHC class II haplotype lost bone marrow engraftment and rejected the VCA graft. Conclusions. – When combined with our prior experiments, our results suggest that some degree of MHC class I matching is necessary for tolerance induction to HCT/VCA, but this is dependent on the degree of class II matching. Full class I matching reliably generates VCA tolerance, regardless of the degree of class II matching. VCA tolerance fails to develop reliably when MHC class I is fully mismatched, regardless of the degree of class II matching. When a single class I haplotype is matched, VCA tolerance depends on the degree of class II matching.