CD8(+) T lymphocytes in double alpha beta TCR transgenic mice. II. Competitive fitness of dual alpha beta TCR CD8(+) T lymphocytes in the peripheral pools
N. Legrand et Aa. Freitas, CD8(+) T lymphocytes in double alpha beta TCR transgenic mice. II. Competitive fitness of dual alpha beta TCR CD8(+) T lymphocytes in the peripheral pools, J IMMUNOL, 167(11), 2001, pp. 6158-6164
We studied Rag2-deficient mice bearing two rearranged ap TCR transgenes, bo
th restricted to the MHC H-2D(b) class I molecule. We have previously shown
that, in these DTg mice, most peripheral CD8 T cells express one TCR beta
chain associated with two TCR alpha chains, as in one-third of the mature T
cells from normal mice. We examined the functional behavior of the dual-re
ceptor CD8 T cells developing either in the absence or in the presence of s
elf-Ag. The dual-receptor CD8 T cells, which develop in absence of self-Ag,
show efficient responses to immunization and remain sensitive to induction
of peripheral tolerance. In contrast to single TCR T cells, the dual-TCR c
ells, when tolerized upon exposure to high levels of self-Ag, are not delet
ed and therefore may exert important regulatory functions. When developing
in the presence of self-Ag, the dual-receptor-expressing CD8 T cells escape
central deletion, but are not fully competent to respond to cognate stimul
i. Overall, we found that the dual-TCR CD8 T cells show a poor competitive
value and can be out-competed by single-TCR cells, both in the course of im
mune responses and in reconstitution experiments. The decreased fitness of
the dual-receptor cells may contribute to diminishing the autoimmune hazard
that they could represent.