期刊
BLOOD
卷 121, 期 12, 页码 2234-2243出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-07-440099
关键词
-
类别
资金
- American Cancer Society
- Children's Cancer Research Fund [P01 CA65493, P01 111412, R01 HL55417, CA72669, PO1067493]
- Children's Cancer Research Fund (ASBMT New Investigators Award)
Human interleukin (IL)-22-producing ROR gamma t(+) innate lymphoid cells (ILC22) and conventional natural killer (cNK) cells are present in secondary lymphoid tissues. Both have an immunophenotype corresponding to stage III NK progenitors (CD56(+/-) CD117(high)CD94(-)). Using an in vitro differentiation and primary human tissues, we investigated their developmental relationships. cNK cells showed a CD56(+)CD117(+)CD7(+/-) LFA-1(high) phenotype and expressed surface receptors, cytokines, and transcription factors found on mature cNK cells. In contrast, ILC22 cells were contained within the CD56(+)CD117(high)CD94(-)CD7(-)LFA-1(-) fraction and produced IL-22, IL-8, and granulocyte macrophage colony stimulating factor. Although ILC22 cells expressed NKp44 and CD161, they lacked most other NK receptors and NK-associated transcription factors (T-bet and Eomes) and were incapable of interferon-gamma production or cytotoxic responses. Most purified CD56(+)CD117(+)CD7(+/-) LFA-1(-) remained as ILC22 cells and never became cNK cells. In the absence of IL-15, CD34(+) cells showed a complete block in cNK differentiation and instead gave rise to a CD56(+) population of ILC22 cells. Conversely, in the absence of IL-7 and stem cell factor, cNK cells were generated but ILC22 cells showed minimal differentiation. Although human ILC22 cells and cNK progenitors have a phenotype that overlaps with stage III NK progenitors, they have unique cytokine requirements and can be distinguished by LFA-1 expression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据