Pj. Fink et al., THE INDUCTION OF PERIPHERAL TOLERANCE BY THE CHRONIC ACTIVATION AND DELETION OF CD4(-BETA-5(+) CELLS()V), The Journal of immunology, 152(9), 1994, pp. 4270-4281
In C57BL/6 mice transgenic for a rearranged gene encoding a V beta 5() beta-chain of the TCR, transgene expression among CD4(+) cells decre
ases with age, such that approximately 40% of CD4(+) cells express an
endogenous beta-chain gene in 8-mo-old mice. A similar deletion of V b
eta 5(+) cells is observed among CD4(+) cells from nontransgenic litte
rmates. V beta 5(+) T cells are deleted intrathymically in I-E(+)Mtv-9
(+) strains of mice, but this chronic deletion occurs in the lymphoid
periphery, in the absence of I-E. We now demonstrate the increased exp
ression of the activation markers CD44 and VLA-4 among CD4(+)V beta 5(
+) cells, in the absence of either an increase in size or IL-2 recepto
r expression. Functional as well as phenotypic differences distinguish
CD4(+) from CD8(+) cells in older V beta 5(+) transgenic mice. Relati
ve to their CD8(+) counterparts, CD4(+)VP beta 5(+) cells are hyporesp
onsive to plate-bound anti-V beta 5 Abs, and this anergy is partially
reversible by the addition of exogenous IL-2. These data suggest the d
eletion of CD4(+)V beta 5(+) cells is the result of a process that inc
ludes their activation, loss of function, and their eventual removal.
To investigate the involvement of the principal V beta 5 superantigen
Mtv-9 in this chronic deletion, we have derived several lines of V bet
a 5(+)I-E(-)Mtv-9(-) mice. Transgene expression also declines with age
in CD4(+) T cells in these mice, clearly demonstrating that the chron
ic deletion of CD4(+)V beta 5(+) cells does not require Mtv-9. There i
s considerable variation in the kinetics and efficiency of CD4(+)V bet
a 5(+) deletion between lines of Mtv-9(-) transgenic mice that is not
from differences in the profiles of endogenous mammary tumor proviruse
s nor readily explained by environmental differences that influence pr
oviral expression. These results suggest the existence of genetic fact
ors other than mammary tumor proviruses that influence the deletion of
CD4(+)V beta 5(+) cells in the absence of I-E.