Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A.
Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A.
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DOI：
10.1371/journal.pone.0031959
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Spee P
中科院分区：
文献类型：
--
作者：
Nielsen N;Ødum N;Ursø B;Lanier LL;Spee P
在慢性炎症性疾病的小鼠模型中，自然杀伤（NK）细胞可以通过消除慢性活化的白细胞来发挥免疫调节作用。间接证据表明NK细胞也可能对人体具有免疫调节作用。人类NK细胞的两个亚群可以在表型上区分为CD 16 + CD 56 dim和CD 16 dim/− CD 56 bright。CD 56 bright NK细胞亚群的扩增与各种自身免疫性疾病治疗的临床反应相关，表明该亚群在体内具有免疫调节作用。在此，我们比较了CD 56 dim和CD 56 bright自体NK细胞在体外对活化的人CD 4 + T细胞的调节。这两个亚群有效地杀死活化的，但不是静止的，CD 4 + T细胞。活化受体NKG 2D，以及整合素LFA-1和TRAIL途径，在这个过程中发挥了重要作用。IL-2、IL-15、IL-12+IL-18和IFN-α可增强NK细胞对活化的CD 4 + T细胞的脱粒作用。有趣的是，IL-7和IL-21刺激CD 56 bright NK细胞的脱粒，但不刺激CD 56 dim NK细胞的脱粒。活化的⑶ 4 + T细胞的NK细胞杀伤被⑶ 4 + T细胞上的HLA-E抑制，因为阻断HLA-E与抑制性⑶ 94/NKG 2A NK细胞受体之间的相互作用增强NK细胞脱粒。这项研究为CD 56 dim和CD 56 bright NK细胞介导的活化自体CD 4 + T细胞的消除提供了新的见解，这可能为慢性炎症的治疗提供了机会。
In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK cells can be phenotypically distinguished as CD16+CD56dim and CD16dim/−CD56bright. An expansion in the CD56bright NK cell subset has been associated with clinical responses to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo. Here we compared the regulation of activated human CD4+ T cells by CD56dim and CD56bright autologous NK cells in vitro. Both subsets efficiently killed activated, but not resting, CD4+ T cells. The activating receptor NKG2D, as well as the integrin LFA-1 and the TRAIL pathway, played important roles in this process. Degranulation by NK cells towards activated CD4+ T cells was enhanced by IL-2, IL-15, IL-12+IL-18 and IFN-α. Interestingly, IL-7 and IL-21 stimulated degranulation by CD56bright NK cells but not by CD56dim NK cells. NK cell killing of activated CD4+ T cells was suppressed by HLA-E on CD4+ T cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK cell receptor enhanced NK cell degranulation. This study provides new insight into CD56dim and CD56bright NK cell-mediated elimination of activated autologous CD4+ T cells, which potentially may provide an opportunity for therapeutic treatment of chronic inflammation.
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影响因子：
4.4
作者：
Dalbeth, N;Gundle, R;Callan, MFC
通讯作者：
Callan, MFC
DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Bielekova, B;Catalfamo, M;Martin, R
通讯作者：
Martin, R
DOI：
10.1084/jem.20051473
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen S;Kawashima H;Lowe JB;Lanier LL;Fukuda M
通讯作者：
Fukuda M
影响因子：
20.3
作者：
Bryceson, Yenan T.;Ljunggren, Hans-Gustaf;Long, Eric O.
通讯作者：
Long, Eric O.
影响因子：
5.4
作者：
Ferlazzo, G;Morandi, B;Moretta, L
通讯作者：
Moretta, L