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.
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.
Miyake
Takashi
T
First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan.
Hosaka
Naoki
N
Cui
Wenhao
W
Nishida
Teruhisa
T
Takaki
Takashi
T
Inaba
Muneo
M
Kamiyama
Yasuo
Y
Ikehara
Susumu
S
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001835:Body Weight; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006087:Graft vs Host Reaction / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D018183:Transplantation Chimera / Q000276:immunology
D016207:Cytokines
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