CD4(+)CD8(+) double-positive thymocytes differentiate into CD4(+) and
CD8(+) single-positive T cells during thymic positive selection. This
process requires the interaction between the TCR and self MHC molecule
s. In this context we have analyzed the expression of CD45, an abundan
t transmembrane protein tyrosine phosphatase, and describe here its di
fferential surface expression during T cell maturation. Using four-col
or FAGS analysis of thymocytes from normal as well as TCR-transgenic m
ice we demonstrate that CD45 is up-regulated only during positive sele
ction concomitantly with the TCR-CD3 complex and the transient early a
ctivation marker long, but that this up-regulation precedes heat stabl
e antigen down-regulation. The tight linkage of the upregulation of th
e TCR-CD3 complex and CD45 may be required because the CD45 tyrosine p
hosphatase plays a role in modulating signal transduction by the TCR-C
D3 complex during positive selection. In addition, our findings argue
for a regulation mechanism that adapts the CD45 levels to increasing a
ntigen receptor levels on mature T cells and B cells.