Coregulation of CXC chemokine receptor and CD4 expression on T lymphocytes during allogeneic activation

Abstract

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.