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Treatment of infectious diseases after organ transplantation using antigen-specific memory T cells in the peripheral blood

利用外周血中抗原特异性记忆T细胞治疗器官移植后的感染性疾病

基本信息

批准号：
17591349
负责人：
TANAKA Kazuo
金额：
$ 2.11万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Animal model : When the BALB/c mice bred under SPF condition were intra-peritoneally infected with 0.2LD50 of murine cytomegalovirus (MCMV), high frequencies of CD69^+/CD44^+ MCMV-specific CD8 T cells were noted in the lungs even at 6 to 12 months after infection (11.1±3.2% and 9.8±0.9%, respectively). In contrast, even though the viral load and expression levels of mRNA of such cytokines as IL-2, IL-7, IL-15 and IFN-γ in the lungs of MCMV-infected OF mice were comparable to those of infected SPF mice, the frequencies of MCMV-specific CD8 T cells in the lungs of infected GF mice were kept lower than 1% at 6 to 12 months after infection. In addition, the reconstitution of microbiota of MCMV-infected GF mice by orally administering a fecal suspension prepared from SPF mice restored both the frequencies of CD8^+/multimer^+ and CD8^+/multimer T cells to levels similar to those found in SPF mice. These results suggested the indigenous microbiota to play a crucial role in the expansion and m … More aintenance of viral specific CD8 memory T cells, probably by cross-reactivity between the antigenic epitope of the MCMV-specific memory T cells and the variety of peptides derived from the members of the microbiota. Such cross-reactivity may thus be a major feature of those cells. Then, we examined to adoptive transfer of the MCMV-specific CD8^+/multimer^+ memory T cells for the treatment of CMV disease, At first, we tried to in vitro expand the MCMV-specific CD8^+/multimer^+ memory T cells, by co-culture with the memory T cells with the antigen-pulsed dentritic cells and such cytokines as IL-2 and /or IL-15. However, we could not in vitro expand the memory T cells under this culture condition.Experiments using human materials : CMV-specific memory T cells were obtained from 20 volunteers, and then in vitro expansion of the memory T cells was done by co-culture with the memory T cells with the antigen-pulsed dentritic cells and IL-2. Memory T cells from the volunteer, who possessed the high frequency of CMV-specific memory T cells (>0.2% of total CD8 cells), could be adequately expanded. However, CMV-specific memory T cells form the other volunteers could not be expanded. Less

动物模型：当在SPF条件下饲养的BALB/c小鼠腹腔内感染0.2LD50的鼠巨细胞病毒（MCMV）时，即使在感染后6至12个月，肺部仍观察到高频率的CD69^+/CD44^+ MCMV特异性CD8 T细胞（分别为11.1±3.2%和9.8±0.9%）。相比之下，尽管感染MCMV的OF小鼠肺中的病毒载量和IL-2、IL-7、IL-15和IFN-γ等细胞因子的mRNA表达水平与感染的SPF小鼠相当，但感染后6至12个月，感染的GF小鼠肺中MCMV特异性CD8 T细胞的频率保持低于1%。此外，通过口服 SPF 小鼠制备的粪便悬浮液来重建 MCMV 感染的 GF 小鼠的微生物群，将 CD8^+/多聚体^+ 和 CD8^+/多聚体 T 细胞的频率恢复到与 SPF 小鼠相似的水平。这些结果表明，本土微生物群在病毒特异性 CD8 记忆 T 细胞的扩增和维持中发挥着至关重要的作用，这可能是通过 MCMV 特异性记忆 T 细胞的抗原表位与源自微生物群成员的各种肽之间的交叉反应来实现的。因此，这种交叉反应性可能是这些细胞的主要特征。然后，我们研究了 MCMV 特异性 CD8^+/multimer^+ 记忆 T 细胞的过继转移用于治疗 CMV 疾病。首先，我们尝试通过将记忆 T 细胞与抗原脉冲的树突状细胞和 IL-2 和/或 IL-15 等细胞因子共培养，在体外扩增 MCMV 特异性 CD8^+/multimer^+ 记忆 T 细胞。然而，我们无法在这种培养条件下体外扩增记忆T细胞。使用人体材料的实验：从20名志愿者中获得CMV特异性记忆T细胞，然后通过将记忆T细胞与抗原脉冲的树突状细胞和IL-2共培养来进行记忆T细胞的体外扩增。来自志愿者的记忆 T 细胞具有高频率的 CMV 特异性记忆 T 细胞（> 总 CD8 细胞的 0.2%），可以充分扩增。然而，来自其他志愿者的 CMV 特异性记忆 T 细胞无法扩增。较少的

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tong, on nitric oxide mediated lung injury in a mouse infected with murine cyteomegalovirus

中药“仁肾养荣通”对小鼠巨细胞病毒感染一氧化氮介导的肺损伤的治疗作用

DOI：
发表时间：
2006
期刊：
International Immunopharmacology 6
影响因子：
0
作者：
Takahashi A;Sato Y;Shiomi Y;et al.;Tanaka et al.
通讯作者：
Tanaka et al.

医学大辞典(第19版)

医学词典（第19版）

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Kawauchi K;Ihjiama K;Yamada O;Tomizawa Y;Shimada T et al.;田中和生(分担)
通讯作者：
田中和生(分担)

CMV感染における免疫応答

CMV 感染的免疫反应

DOI：
发表时间：
2006
期刊：
日本臨床 64
影响因子：
0
作者：
野田敏司;田中和生
通讯作者：
田中和生

Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito) on nitric oxide-mediated lung injury in a mouse infected with murine cytomegalovirus

DOI：
10.1016/j.intimp.2005.10.011
发表时间：
2006-04-01
期刊：
INTERNATIONAL IMMUNOPHARMACOLOGY
影响因子：
5.6
作者：
Tanaka, K;Sawamura, S
通讯作者：
Sawamura, S

Cytomegalovirus MCK-2 controls mobilization and recruitement of myeloid progenitor cells to facilitate dissemination

巨细胞病毒 MCK-2 控制骨髓祖细胞的动员和募集以促进传播

DOI：
发表时间：
2006
期刊：
Blood 107
影响因子：
0
作者：
Kasahara M;Ueda M;Haga H;Hiramatsu H;Kobayashi M;Adachi S;Sakamoto S;Oike F;Egawa H;Takada Y;Tanaka K;Noda et al.
通讯作者：
Noda et al.