Resistance of KIR ligand-missing leukocytes to natural killer cells in vivo in patients with acquired aplastic anemia

フォーマット:

論文

責任表示:

Nguyen Thi, Mai Anh ; Hosokawa, Kohei ; Yoroidaka, Takeshi ; Maruyama, Hiroyuki ; Espinoza, J. Luis ; Elbadry, Mahmoud I. ; Md, Mohiuddin ; Tanabe, Mikoto ; Katagiri, Takamasa ; Nakagawa, Noriharu ; Arima, Nobuyoshi ; Kashiwase, Koichi ; Saji, Hiroh ; Ogawa, Seishi ; Nakao, Shinji ; 細川, 晃平 ; 片桐, 孝和 ; 中尾, 眞二

言語:

英語

出版情報:

The American Association of Immunologists, 2020-07-01

著者名:

Nguyen Thi, Mai Anh

Hosokawa, Kohei

Yoroidaka, Takeshi

Maruyama, Hiroyuki

Espinoza, J. Luis

Elbadry, Mahmoud I.

Md, Mohiuddin

Tanabe, Mikoto

Katagiri, Takamasa

Nakagawa, Noriharu

Arima, Nobuyoshi

Kashiwase, Koichi

Saji, Hiroh

Ogawa, Seishi

Nakao, Shinji

細川, 晃平

片桐, 孝和

中尾, 眞二

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掲載情報:

ImmunoHorizons

ISSN:

2573-7732      

巻:

4

通号:

7

開始ページ:

430

終了ページ:

441

バージョン:

author

概要:

金沢大学医薬保健研究域医学系　Graduate School of Medical Sciences<br />The loss of killer cell immunoglobulin-like receptor-ligands (KIR-Ls) due to the copy number neutral loss of heterozygosity of chromosome 6p (6pLOH) in leukocytes of patients wit … h acquired aplastic anemia (AA) may alter the susceptibility of the affected leukocytes to NK cell killing in vivo. We studied 408 AA patients, including 261 who were heterozygous for KIR-Ls, namely C1/C2 or Bw6/Bw4, for the presence of KIR-L-missing (KIR-L[-]) leukocytes. KIR-L(-) leukocytes were found in 14 (5.4%, C1, n= 4, C2, n=3, and Bw4, n= 7) of the 261 patients, in whom corresponding KIR(+) licensed NK cells were detected. The incidence of 6pLOH in the 261 patients (18.0%) was comparable to that in 147 patients (13.6%) who were homozygous for KIR-L genes. The percentages of HLA-lacking granulocytes (0.8-50.3%, median 15.2%) in the total granulocytes of the patients with KIR-L(-) cells were significantly lower than those (1.2-99.4%, median 55.4%) in patients without KIR-L(-) cells. KIR2DS1 and KIR3DS1 were only possessed by three of the 14 patients, two of whom had C2/C2 leukocytes after losing C1 alleles. The expression of the KIR3DS1 ligand HLA-F was selectively lost on KIR-L(-) primitive hematopoietic stem cells (HSCs) derived from 6pLOH(+) iPS cells in one of the KIR3DS1(+) patients. These findings suggest that human NK cells are able to suppress the expansion of KIR-L(-) leukocytes but are unable to eliminate them partly due to the lack of activating KIRs on NK cells and the low HLA-F expression level on HSCs in AA patients.<br />Embargo Period 6 months 続きを見る

URL:

http://hdl.handle.net/2297/00058826