We describe a novel CD8(+)NKT cell population expressing TCR alpha/beta or
TCR gamma/delta. These CD8(+)NKT cells were prominent in the liver, and exc
ept for the thymus, virtually absent in other lymphoid organs. CD8(+)NKT ce
lls expressed activation markers and comprised a high proportion of Ly49(+)
cells. The development of the majority of CD8(+)NKT cells expressing TCR a
lpha/beta, but not TCR gamma/delta, depended on classical MHC class I. No C
D8(+)NKT cells were detectable in young athymic mice, whereas the cells exp
ressing TCR gamma/delta, but not TCR alpha/beta, appeared randomly in aged
athymic mice. CD8(+)NK1(+) TCR alpha/beta cells showed polyclonal TCRV beta
usage and were virtually devoid of TCRV alpha 14. CD8(+)NK1(+) TCR gamma/d
elta cells predominantly expressed TCRV gamma 1, 2 and 4, and V delta 4, 5,
6 and 7. CD8(+)NKT cells, in particular those expressing TCR gamma/delta,
were a major population in early life. IFN-gamma, but not IL-4, was induced
in CD8(+)NKT cells by in vitro stimulation, independent of the TCR alpha/b
eta or TCR gamma/delta lineage, Hence, these cells represent a unique, thou
gh heterogeneous T cell population that shares markers with, but is distinc
t from, both conventional NKT cells and conventional CD8(+) T cells, and th
at may play a role in immune regulation.