A. Hameg et al., A subset of NKT cells that lacks the NK1.1 marker, expresses CD1d molecules, and autopresents the alpha-galactosylceramide antigen, J IMMUNOL, 165(9), 2000, pp. 4917-4926
In the present report, we characterize a novel T cell subset that shares wi
th the NKT cell lineage both CD1d-restriction and high reactivity in vivo a
nd in vitro to the alpha -galactosylceramide (alpha -GalCer) glycolipid. Th
ese cells preferentially use the canonical V alpha 14-J alpha 281 TCR-alpha
-chain and vps TCR-beta segments, and are stimulated by alpha -GalCer in a
CD1d-dependent fashion. However, in contrast to classical NKT cells, they
lack the NK1.1 marker and express high surface levels of CD1d molecules. In
addition, this NK1.1(similar to) CD1d(high) T subset, further referred to
as CD1d(high) NKT cells, can be distinguished by its unique functional feat
ures. Although NK1.1(+) NKT cells require exogenous CD1d-presenting cells t
o make them responsive to alpha -GalCer, CD1d(high) NKT cells can engage th
eir own surface CD1d in an autocrine and/or paracrine manner. Furthermore,
in response to alpha -GalCer, CD1d(high) NKT cells produce high amounts of
IL-4 and moderate amounts of IFN-gamma, a cytokine profile more consistent
with a Th2-like phenotype rather than the Th0-like phenotype typical of NK1
.1(+) NKT cells. Our work reveals a far greater level of complexity within
the NKT cell population than previously recognized and provides the first e
vidence for T cells that can be activated upon TCR ligation by CD1d-restric
ted recognition of their ligand in the absence of conventional APCs.