CYTOTOXICITY OF FRESH NK1.1(-CELL RECEPTOR ALPHA() T)BETA(+) THYMOCYTES AGAINST A CD4+8+ THYMOCYTE POPULATION ASSOCIATED WITH INTACT FAS ANTIGEN EXPRESSION ON THE TARGET/
H. Arase et al., CYTOTOXICITY OF FRESH NK1.1(-CELL RECEPTOR ALPHA() T)BETA(+) THYMOCYTES AGAINST A CD4+8+ THYMOCYTE POPULATION ASSOCIATED WITH INTACT FAS ANTIGEN EXPRESSION ON THE TARGET/, The Journal of experimental medicine, 180(2), 1994, pp. 423-432
Recent studies have revealed that 10-20% of CD4(+)8(-) or CD4(-)8(-) t
hymocyte populations contain NK1.1(+) T cell receptor (TCR)alpha/beta(
+) cells. This subpopulation shows characteristics that are different
from NK1.1(-) CD4(+) or NK1.1(-) CD8(+) T cells and seems to have deve
loped in a manner different from NK1.1(-) T cells. Although extensive
studies have been performed on the NK1.1(+) TCR-alpha/beta(+) thymocyt
es, the physiological role of the NK1.1(+) TCR-alpha/beta(+) thymocyte
s has been totally unclear. In the present study, we found that freshl
y isolated NK1.1(+) TCR-alpha/beta(+) thymocytes, but neither whole th
ymocytes nor lymph node T cells, directly killed CD4(+)8(+) thymocytes
from normal syngeneic or allogeneic mice by using a long-term cytotox
ic assay in which flow cytometry was used to detect the cytotoxicity.
However, only weak cytotoxicity was detected against thymocytes from l
pr mice on which the Fas antigen that transduces signals for apoptosis
into the cells is not expressed. Furthermore, the NK1.1(+) TCR-alpha/
beta(+) thymocytes exhibited high cytotoxicity against T lymphoma targ
ets transfected with fas genes as compared with the parental T lymphom
a targets or target cells transfected with mutated fas genes, which la
ck the function of transducing signals. On the other hand, NK1.1(+) ef
fector thymocytes from gld mice that carry a point mutation in Fas lig
and did not kill thymocyte targets from normal mice. The present findi
ngs, thus, consistently suggest that the NK1.1(+) TCR-alpha/beta(+) th
ymocytes kill a subpopulation among CD4(+)8(+) thymocytes via Fas anti
gen and in this way regulate generation of T lineage cells in the thym
us.