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Adult thymus transplantation with allogeneic intra‐bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft‐versus‐host reaction and strong graft‐versus‐tumour effects
Author(s) -
Miyake Takashi,
Hosaka Naoki,
Cui Wenhao,
Nishida Teruhisa,
Takaki Takashi,
Inaba Muneo,
Kamiyama Yasuo,
Ikehara Susumu
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02920.x
Subject(s) - bone marrow , medicine , transplantation , donor lymphocyte infusion , cd8 , leukemia , immunology , foxp3 , tunel assay , graft versus host disease , pathology , andrology , immune system , immunohistochemistry
Summary Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft‐versus‐tumour (GVT) effects, a graft‐versus‐host reaction (GVHR) is also elicited. We carried out intra‐bone marrow–bone marrow transplantation (IBM‐BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM‐BMT + ATT survived for a long time with high donor‐derived thymopoiesis and mild GVHR. The percentage of CD4 + FoxP3 + regulatory T cells in the spleen of the mice treated with IBM‐BMT + ATT was lower than in normal B6 mice or mice treated with IBM‐BMT alone, but higher than in mice treated with IBM‐BMT + DLI; the mice treated with IBM‐BMT + DLI showed severe GVHR. In tumour‐bearing mice, tumour growth was more strongly inhibited by IBM‐BMT + ATT than by IBM‐BMT alone. Mice treated with IBM‐BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM‐BMT + ATT but died early of GVHD. By contrast, mice treated with IBM‐BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM‐BMT + ATT. Histologically, significant numbers of CD8 + T cells were found to have infiltrated the tumour in the mice treated with IBM‐BMT + ATT. The number of terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labelling (TUNEL)‐positive apoptotic tumour cells also significantly increased in the mice treated with IBM‐BMT + ATT. Allogeneic IBM‐BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR.