Cytokine-polarized T cells have distinct chemokine receptor (CKR) expression patterns associated with their cytokine secretion profiles. In order to investigate this paradigm in autoreactive human T cells, we have determined the CKR expression pattern of myelin basic protein (MBP)-reactive T cell lines (TCL) and compared these profiles to those of TCL-generated in response to tetanus toxoid (TT). Expression of CXCR6 and CXCR3 on TCL was significantly positively correlated with IFNgamma, and inversely correlated with IL-5 production. TT TCL had significantly higher expression of CCR7(-)/CD45RA(-) T effector memory (Tem) cells than MBP TCL. However, in MBP-specific TCL, CXCR6 was found to be the best marker of conversion to the Tem phenotype. CXCR6 and CXCR3 are likely to be important in the migration of effector memory T cells in Th1-mediated inflammatory diseases such as multiple sclerosis (MS).