Voyle Roger B, Beermann Friedrich, Lees Rosemary K, Schümann Jens, Zimmer Jacques, Held Werner, MacDonald H Robson
Ludwig Institute for Cancer Research, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
J Exp Med. 2003 Apr 7;197(7):919-25. doi: 10.1084/jem.20021615.
In addition to their CD1d-restricted T cell receptor (TCR), natural killer T (NKT) cells express various receptors normally associated with NK cells thought to act, in part, as modulators of TCR signaling. Immunoreceptor-tyrosine activation (ITAM) and inhibition (ITIM) motifs associated with NK receptors may augment or attenuate perceived TCR signals respectively, potentially influencing NKT cell development and function. ITIM-containing Ly49 family receptors expressed by NKT cells are proposed to play a role in their development and function. We have produced mice transgenic for the ITAM-associated Ly49D and ITIM-containing Ly49A receptors and their common ligand H2-Dd to determine the importance of these signaling interplays in NKT cell development. Ly49D/H2-Dd transgenic mice had selectively and severely reduced numbers of thymic and peripheral NKT cells, whereas both ligand and Ly49D transgenics had normal numbers of NKT cells. CD1d tetramer staining revealed a blockade of NKT cell development at an early precursor stage. Coexpression of a Ly49A transgene partially rescued NKT cell development in Ly49D/H2-Dd transgenics, presumably due to attenuation of ITAM signaling. Thus, Ly49D-induced ITAM signaling is incompatible with the early development of cells expressing semi-invariant CD1d-restricted TCRs and appropriately harmonized ITIM-ITAM signaling is likely to play an important role in the developmental program of NKT cells.
除了其受CD1d限制的T细胞受体（TCR）外，自然杀伤T（NKT）细胞还表达多种通常与NK细胞相关的受体，这些受体被认为部分作为TCR信号的调节剂。与NK受体相关的免疫受体酪氨酸激活（ITAM）和抑制（ITIM）基序可能分别增强或减弱所感知的TCR信号，潜在地影响NKT细胞的发育和功能。有人提出，NKT细胞表达的含ITIM的Ly49家族受体在其发育和功能中起作用。我们已经培育出了携带与ITAM相关的Ly49D和含ITIM的Ly49A受体及其共同配体H2-Dd的转基因小鼠，以确定这些信号相互作用在NKT细胞发育中的重要性。Ly49D/H2-Dd转基因小鼠的胸腺和外周NKT细胞数量选择性地严重减少，而配体和Ly49D转基因小鼠的NKT细胞数量正常。CD1d四聚体染色显示在早期前体阶段NKT细胞发育受阻。Ly49A转基因的共表达部分挽救了Ly49D/H2-Dd转基因小鼠的NKT细胞发育，推测这是由于ITAM信号的减弱。因此，Ly49D诱导的ITAM信号与表达半不变CD1d限制TCR的细胞的早期发育不相容，适当协调的ITIM-ITAM信号可能在NKT细胞的发育程序中起重要作用。
