Switch in chemokine receptor phenotype on memory T cells without a change in the cytokine phenotype

Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors CCR5 and CCR3, respectively. In c ommitted human memory Th1 cells the cytokine profile is irreversibly expres sed. However, it is not known if the chemokine receptor phenotypes of Th1 a nd Th2 cells are permanently associated to the cytokine profile or if it ca n be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cell s isolated from synovial tissue (ST) samples of patients with rheumatoid ar thritis (RA), Freshly isolated T cells, T-cell Lines and T-cell clones from these tissues were manipulated with Th1 (interleukin (IL)-12 + anti IL-4) or Th2 (IL-4 + anti IL-12) inducing conditions. The surface expression of C CR5 and CCR3 was analyzed by flowcytometry and interferon (IFN)-gamma and I L-4 production by ELISA, A Th1-inducing cytokine environment increased the expression of CCR5 in Th1 cells and induced the expression of CCR5 in Th2 c ells as compared to culture condition with only IL-2, Induction of CCR5 exp ression on Th2 clones was associated with secretion of some IFN-gamma. More over, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture cond itions with IL-4,This expression of CCR3 was associated with a reduced IFN- gamma production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, thr same I L-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a c hange in chemokine receptor phenotype related to the Th2 type can be induce d on terminally differentiated Th1 cells, without a change in the cytokine profile.