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Graft‐Versus‐Host Disease Following Liver Transplantation: Development of a High‐Incidence Rat Model and a Selective Prevention Method
Author(s) -
Yu E.,
Ueta H.,
Kimura H.,
Kitazawa Y.,
Sawanobori Y.,
Matsuno K.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14077
Subject(s) - graft versus host disease , immunology , medicine , cd8 , transplantation , il 2 receptor , ex vivo , liver transplantation , t cell , immune system , in vivo , biology , microbiology and biotechnology
Graft‐versus‐host disease (Gv HD ) following liver transplantation ( LT ) is a rare but serious complication with no presently available animal model and no preventive measures. To develop a rat model of Gv HD after LT ( LT ‐Gv HD ), we preconditioned hosts with sublethal irradiation plus reduction of natural killer (NK) cells with anti‐ CD 8α mA b treatment, which invariably resulted in acute LT ‐Gv HD . Compared with those in the peripheral counterpart, graft CD 4 + CD 25 − passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD 4 + T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs. For selectively preventing Gv HD , donor livers were perfused ex vivo with organ preservation media containing anti‐ TCR αβ mA b. T cell–depleted livers almost completely suppressed clinical Gv HD such that host rats survived for >100 days. Our results showed that passenger T cells could develop typical LT ‐Gv HD if resistant cells such as host radiosensitive cells and host radioresistant NK cells were suppressed. Selective ex vivo T cell depletion prevented LT ‐Gv HD without affecting host immunity or graft function. This method might be applicable to clinical LT in prediagnosed high‐risk donor–recipient combinations and for analyzing immunoregulatory mechanisms of the liver.