Among the T cell pool of multiple specificities in the rheumatoid synovial tissues (ST) we have previously shown a lack of proliferative response of T cells to Acanthamoeba polyphaga [1]. In contrast, peripheral blood (PB) derived T cells proliferate to the antigen. The aim of the present study was to establish whether there is a preferential migration of some T cell specificities to the joint in rheumatoid arthritis (RA) patients dependent on the chemokine system, and to identify which chemokine receptors are involved in the migratory process. For this purpose, PB-derived T cell lines and clones from RA patients specific for A. polyphaga, herpes simplex virus (HSV) and Campylobacter jejuni were developed. Their migratory capacities towards ST-derived chemokine supernatants were analysed. Expression of CCR1, CCR2, CCR5, CCR6, CCR7, CXCR3 and CXCR4 were analysed by FACS, and attracting chemokines were identified by blocking studies. We found that the migratory capacities of T cells specific for C. jejuni and HSV were markedly higher against synovial chemokines than T cells specific for A. polyphaga. CCR5 and CXCR3 were expressed by all high-migrating T cell lines and clones. CCR2 was expressed at higher levels on the high-migrating T cell lines compared with the low-migrating A. polyphaga lines. Neutralization of RANTES (regulated upon activation normal T cell expressed and secreted) in the ST cell-derived supernatant reduced T cell migration of all T cell lines and clones by 60-90%, while neutralization of MCP-1 reduced the migratory capacity of CCR2-expressing T cells by 45-80%. In conclusion, the ability of T cells to migrate towards chemokines produced by ST cells is associated with the T cell specificity. Blocking of single chemokines substantially reduced the migratory capacity of memory T cells to ST cell-derived supernatant indicating unique roles for each chemokine receptor in the process of T cell migration.