
<ArticleTitle>Switch in chemokine receptor phenotype on memory T cells without a change in the cytokine phenotype.</ArticleTitle>
<AbstractText>Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors <prot>CCR5</prot> and <prot>CCR3</prot>, respectively. In committed human memory Th1 cells the cytokine profile is irreversibly expressed. However, it is not known if the chemokine receptor phenotypes of Th1 and Th2 cells are permanently associated to the cytokine profile or if it can be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cells isolated from synovial tissue (ST) samples of patients with rheumatoid arthritis (RA). Freshly isolated T cells, T-cell lines and T-cell clones from these tissues were manipulated with Th1 (<prot>interleukin (IL)-12</prot> + anti <prot>IL-4</prot>) or Th2 (<prot>IL-4</prot> + anti <prot>IL-12</prot>) inducing conditions. The surface expression of CCR5 and CCR3 was analyzed by flowcytometry and <prot>interferon (IFN)-gamma</prot> and <prot>IL-4</prot> production by ELISA. A Th1-inducing cytokine environment increased the expression of <prot>CCR5</prot> in Th1 cells and induced the expression of <prot>CCR5</prot> in Th2 cells as compared to culture condition with only <prot>IL-2</prot>. Induction of <prot>CCR5</prot> expression on Th2 clones was associated with secretion of some <prot>IFN-gamma</prot>. Moreover, the Th2-associated chemokine receptor <prot>CCR3</prot> could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with <prot>IL-4</prot>. This expression of <prot>CCR3</prot> was associated with a reduced <prot>IFN-gamma</prot> production, but no <prot>IL-4</prot> production could be induced. The <prot>IL-4</prot>-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same <prot>IL-12</prot>-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker <prot>CCR3</prot> on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.</AbstractText>
