Introduction
Some while ago we reported that most early thymic progenitor cells have
the capacity to develop autonomously into functional NK cells under defined
in vitro conditions, thereby providing a potentially powerful system for
studying the critical events that occur during NK cell differentiation
[Brooks et al. J. Immunol. 151, 6645, 1993]. The NK cells that develop
under these conditions show heterogeneous expression of various surface
molecules involved in intercellular recognition, including Ly6, various
CD45 isoforms, NKRP1 molecules, and receptors for the non-classical class
I molecule Qa1, each of which is acquired in a stochastic manner [Manoussaka
et al. J. Immunol. 158, 112, 1997; Toomey et al. J. Immunol. 163, 3176,
1999]. As in the case of NK cells that develop from bone-marrow progenitors
in the absence of stromal cells [Williams et al. J. Exp. Med. 186, 1609,
1997], very few of the NK cells that develop autonomously from early thymic
progenitors express any of several Ly49 molecules that have previously
been examined, either at the cell surface or at the mRNA level. However,
two exceptions to this have been noted. Firstly, some clones and
lines that develop from fetal progenitors contain small numbers of cells
that express Ly49C/I or G, suggesting that the Ly49 genes in these cells
are in a potentially expressible state [Manoussaka et al. J. Immunol. 158,
112, 1997]. Secondly, abundant levels of mRNA for Ly49E have been
found in these cells [Toomey et al. Eur. J. Immunol. 28, 47, 1998].
We report here that the majority of NK cells that develop in vitro from
thymus progenitors in fact express high levels of previously uncharacterized
Ly49 molecules, most likely Ly49E, on their surfaces. We also show
that these Ly49 molecules are acquired in a progressive and stochastic
manner independently of CD94 and NKG2 molecules, and that the expression
of Ly49 and CD94 receptors, but not NKRP1 molecules, is differentially
regulated by IL4.