- 作者：Naoko Kutsuna ; M.D. ; Shintaro Yamazaki ; M.D. ; Ph.D. ; yamazaki-nmed@umin.ac.jp ; Teruo Kaiga ; M.D. ; Ph.D. ; Yoshinori Inagaki ; Ph.D. ; Yuki Hayashi ; M.D. ; Ph.D. ; Shunji Okada ; M.D. ; Ph.D. ; Akira Kanamoto ; M.D. ; Ph.D. ; Tadatoshi Takayama ; M.D. ; Ph.D.
- 关键词：bone marrow ; chimerism ; donor-specific tolerance ; skin graft ; splenocyte
- 刊名：Journal of Surgical Research
- 出版年：2012
- 出版时间：1 June, 2012
- 年：2012
- 卷：175
- 期：1
- 页码：62-66
- 全文大小：312 K
Background
We have shown that partially major histocompatibility complex (MHC)-matched splenocytes can replace bone marrow (BM) and maintain skin grafts by establishing splenocytic chimeras. Our aim was to identify the population of splenocytes that are indispensible for switching from BM to splenocytic chimerism.Methods
C3H/B6D2F1 mixed BM chimeras were established in lethally irradiated C3H mice. Skin grafts from C57BL/6 mice were transplanted 30 d later. After an additional 30 d, splenocytes from B6C3F1 mice were transplanted to establish splenocytic BM chimeras using total splenocytes (group A), CD90+-depleted splenocytes (group B), CD4+-depleted splenocytes (group C), or CD8+-depleted splenocytes (group D).
Results
In group A, the BM switched to splenocyte-derived BM chimeras. Total B6C3F1 splenocytes created stable splenocyte BM chimeras that permitted long-term retention of skin grafts, without rejection. In groups B and D, the splenocytes failed to replace the recipient BM, and there was no decrease in the?number of recipient-derived BM cells compared with group A from d 14 to 28 after splenocyte injection, as was the case for CD8+ T cells. In group C mice, the recipient BM was slowly and incompletely replaced.
Conclusions
Partially MHC-matched donor CD8+ T?cells are indispensable for generating splenocyte chimeras in BM and maintaining allogeneic skin grafts.