Shimada Shin, Nunomura Satoshi, Mori Shuya, Suemizu Hiroshi, Itoh Toshio, Takabayashi Shuji, Okada Yoshinori, Yahata Takashi, Shiina Takashi, Katoh Hideki, Suzuki Ryuji, Tani Kenzaburo, Ando Kiyoshi, Yagita Hideo, Habu Sonoko, Sasaki Erika, Kametani Yoshie
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Japan.
Division of Molecular Cell Immunology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan.
Int Immunol. 2015 Nov;27(11):567-77. doi: 10.1093/intimm/dxv031. Epub 2015 May 14.
Analysis of the hematopoiesis of non-human primates is important to clarify the evolution of primate-specific hematopoiesis and immune regulation. However, the engraftment and development of the primate hematopoietic system are well-documented only in humans and are not clear in non-human primates. Callithrix jacchus (common marmoset, CM) is a New World monkey with a high rate of pregnancy and small size that lives in closed colonies. As stem cell factor (SCF) is an essential molecule for hematopoietic stem cell development in mice and humans, we focused on CD117, the SCF receptor, and examined whether CD117-expressing cells possess the hematopoietic stem/progenitor cell characteristics of newborn marmoset-derived hematopoietic cells that can develop into T cells and B cells. When CD117(+) cell fractions of the bone marrow were transplanted into immunodeficient NOD (non-obese diabetic)/Shi-scid, common γc-null (NOG) mice, these cells engrafted efficiently in the bone marrow and spleens of the NOG mice. The CD117(+) cells developed into myeloid lineage cells, CD20(+) B cells and CD3(+) T cells, which could express CM cytokines in vivo. The development of B cells did not precede that of T cells. The development of CD8(+) T cells was dominant in NOG mice. The engraftment was comparable for both CD117(+)CD34(+) cells and CD117(+)CD34(-) cells. These results suggest that the CD117(+) cell fraction can differentiate into all three cell lineages, and the development of marmoset immunity in the xenogeneic environment follows diverse developmental pathways compared with human immunity.
对非人类灵长类动物造血作用的分析，对于阐明灵长类动物特有的造血作用和免疫调节的进化过程具有重要意义。然而，灵长类造血系统的植入和发育情况仅在人类中有充分记录，在非人类灵长类动物中尚不清楚。普通狨猴（Callithrix jacchus，CM）是一种新大陆猴，妊娠率高且体型小，生活在封闭群体中。由于干细胞因子（SCF）是小鼠和人类造血干细胞发育的必需分子，我们聚焦于SCF受体CD117，并研究表达CD117的细胞是否具有新生狨猴来源的造血细胞的造血干/祖细胞特征，这些造血细胞可发育为T细胞和B细胞。当将骨髓中CD117(+)细胞组分移植到免疫缺陷的NOD（非肥胖糖尿病）/Shi-scid、普通γc基因敲除（NOG）小鼠体内时，这些细胞能有效地植入到NOG小鼠的骨髓和脾脏中。CD117(+)细胞发育为髓系细胞、CD20(+) B细胞和CD3(+) T细胞，这些细胞在体内可表达狨猴细胞因子。B细胞的发育并不先于T细胞。在NOG小鼠中，CD8(+) T细胞的发育占主导地位。CD117(+)CD34(+)细胞和CD117(+)CD34(-)细胞的植入情况相当。这些结果表明，CD117(+)细胞组分可分化为所有三种细胞谱系，与人类免疫相比，狨猴免疫在异种环境中的发育遵循不同的发育途径。
