Functional and phenotypic analysis of human memory CD8⁺ T cells expressing CXCR3

Several chemokine receptors play an important role in the migration of naïve, memory, and effector T cells. Flow cytometric analyses showed that human CD8⁺ T cells with naïve (CD27⁺CD28 ⁺CD45RA⁺) or memory (CD27⁺CD28 ⁺/^-CD45RA⁺) phenotypes included a population expressing a high level of CXC chemokine receptor 3 (CXCR3^high) and one expressing a low level of it (CXCR3^low), but those with the effector phenotype (CD27^-CD28^-CD45RA^+/-) included a population that did not express CXCR3 (CXCR3^-) and a CXCR3^low population. This relation between the expression level of CXCR3 and memory/effector phenotypes also applied to Epstein-Barr virus- or human cytomegalovirus-specific CD8⁺ T cells. CXCR3^high cells were found predominantly in CC chemokine receptor 7 (CCR7) ⁺CCR5^- and CCR7^-CCR5^- subsets of CD8⁺ T cells with the CD27⁺CD28⁺CD45RA ^- memory phenotype, suggesting that they are memory cells with intermediate differentiation. Indeed, CXCR3^highCD27 ⁺CD28⁺CD45RA^--CD8⁺ T cells had the ability to produce interleukin-2 and interferon-γ. These results together indicate that the expression of CXCR3 is upregulated on intermediately differentiated memory CD8⁺ T cells. CXCR3^highCD8 ⁺ T cells had a greater ability to migrate in response to CXCR3 ligands than CXCR3^low ones. As CXCR3^high memory CD8 ⁺ T cells do not express CCR5, high expression of CXCR3 on these memory CD8⁺ T cells might play an important role in the migration of these cells to inflammatory sites and in their differentiation.