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Chemokine Biology Laboratory, Department of Molecular Biosciences, Adelaide University, South Australia, Australia
Upon activation, naive T cells alter their migratory patterns,
acquiring the ability to move through peripheral tissues as well as the
general lymphoid circulation. Although the mechanisms responsible for
these alterations are not well understood, changes in chemokine
receptor expression may play a critical role. To investigate these
changes, the expression patterns of two chemokine receptors, CXCR3 and
CXCR4, were compared on CD4+ T cells following activation
in the MLR. By day 9 of activation, expression of the inflammatory
chemokine receptor CXCR3 was up-regulated, while expression of the
homeostatic chemokine receptor CXCR4 was down-regulated. Alterations in
receptor expression occurred almost exclusively on a subpopulation of T
cells that expressed higher levels of CD4. These CD4high T
cells demonstrated many characteristics of activated T cells and had
undergone division in the MLR. By day 9 of culture, the majority of
CXCR3+ and CXCR4- cells had divided and had
acquired an activated/memory phenotype (CD45RA-
CD45RO+ CD69+ CD25+). The
levels of transcripts for both CXCR3 and CXCR4 were increased upon
allo-activation. The discrepancy between levels of CXCR4 mRNA and
surface protein was not due to sequestration of the receptor in
intracellular compartments, as CXCR4 was not detectable
intracellularly. However, intracellular CXCR3 was readily detectable.
Finally, cells from allogeneic cultures demonstrated enhanced migration
toward IFN-inducible T cell 
chemoattractant and reduced migration
toward stromal cell-derived factor-1 compared with syngeneic controls,
thus suggesting that the observed switch in receptor expression may at
least partly contribute to the differential patterns of migration
displayed by naive and memory T cells.
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