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Expression and Signaling in Early Thymocytes Impair Thymocyte Expansion and Partially Block Their Development
ek-Szabo*
2,*
ugich3,*,
*
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, and
Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021
In thymocyte ontogeny, Tcr-a genes rearrange after
Tcr-b genes. TCR
transgenic (Tg) mice have no such
delay, consequently expressing rearranged TCR proteins early in
the ontogeny. Such mice exhibit reduced thymic cellularity and
accumulate mature, nonprecursor
TCR+CD8-4- thymocytes, believed
to be caused by premature Tg TCR expression via unknown
mechanism(s). Here, we show that premature expression of TCR on
early thymocytes curtails thymocyte expansion and impairs the
CD8-4- 
CD8+4+
transition. This effect is accomplished by two distinct mechanisms.
First, the early formation of TCR appears to impair the formation
and function of pre-TCR, consistent with recently published results.
Second, the premature TCR contact with intrathymic MHC molecules
further pronounces the block in proliferation and differentiation.
These results suggest that the benefit of asynchronous
Tcr-a and Tcr-b rearrangement is not only
to minimize waste during thymopoiesis, but also to simultaneously allow
proper expression/function of the pre-TCR and to shield
CD8-4- thymocytes from TCR signals that
impair thymocyte proliferation and CD8-4-
CD8+4+ transition.
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