THE DEGREE OF CD8 DEPENDENCE OF CYTOLYTIC T-CELL PRECURSORS IS DETERMINED BY THE NATURE OF THE T-CELL RECEPTOR (TCR) AND INFLUENCES NEGATIVE SELECTION IN TCR-TRANSGENIC MICE
N. Auphan et al., THE DEGREE OF CD8 DEPENDENCE OF CYTOLYTIC T-CELL PRECURSORS IS DETERMINED BY THE NATURE OF THE T-CELL RECEPTOR (TCR) AND INFLUENCES NEGATIVE SELECTION IN TCR-TRANSGENIC MICE, European Journal of Immunology, 24(7), 1994, pp. 1572-1577
Although much has been learned about CD8 structure-function properties
, it has so far not been tested whether the nature of the TCR is suffi
cient to transfer the property of CD8 dependence versus non-dependence
to CD8(+) cytotoxic T lymphocytes (CTL) and their precursors differen
tiating in T cell receptor (TCR)-transgenic (Tg) mice. In the present
study, we compared the characteristics of dependence on CD8 for stimul
ation of CTL precursors and antigen-specific cytolysis by CD8(+) T cel
ls from two TCR-Tg mice expressing respectively the TCR (Tg) from a ''
CD8-dependent'' and from a ''CD8-independent'' CTL clone, which were b
oth reactive against the H-2K(b) alloantigen and originated from H-2(k
) mice. The results indicate that the property of the Tg(+)CD8(+) cell
s from H-2(k) TCR-Tg mice corresponds to that of the CTL clone of orig
in, demonstrating that it is linked to the nature of the TCR. Consiste
nt with this property, Tg(+)CD4(+) cells could also differentiate into
H-2K(b)-specific CTL when originating from the ''CD8-independent'', b
ut not from the ''CD8-dependent'' Tg-TCR. The influence of the propert
y of ''CD8 dependence'' on negative selection occurring in TCR-Tg H-2(
k/b) mice was apparent at two levels: (i) in the thymus, the extent of
deletion was much more pronounced for the ''CD8-independent'' TCR-Tg
mice; (ii) in the periphery, Tg(+(hi)) cells with low to negative CD8
expression were present for the ''CD8-dependent'' Tg-TCR, whereas only
Tg(+)CD4(-)CD8(-) cells with low surface Tg-TCR and CD3 expression we
re found for the ''CD8-independent'' Tg-TCR, indicating that Tg(+)CD4(
-)CD8(-) cells are susceptible to tolerance induction involving TCR/CD
3 surface down-modulation, Furthermore, different in vitro conditions
led to H-2K(b)-induced stimulation of Tg(+)CD4(-)CD8(-) cells to diffe
rentiate into CTL detected in an anti-TCR clonotypic monoclonal antibo
dy redirected cytolysis assay. Culture in interleukin-2 of H-2(k/b) Tg
(+)CD4(-)CD8(-) cells was sufficient to induce CTL activity in the ''C
D8-independent'' model, whereas stimulation with cells which overexpre
ssed H-2K(b) was required in addition to interleukin-2 to induce CTL d
ifferentiation in the ''CD8-dependent'' model. These data suggest that
peripheral Tg(+)CD4(-)CD8(-) cells present in a situation of in vivo
tolerance to H-2K(b) can still be triggered by H-2K(b) with a sensitiv
ity correlated with the degree of CD8 dependence.