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(Journal of Leukocyte Biology. 2006;80:320-329.)
© 2006 by Society for Leukocyte Biology

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

Naoki Kobayashi^*,, Takaaki Kondo^*, Hiroshi Takata^*, Shumpei Yokota and Masafumi Takiguchi^*,1

^* Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Japan; and
Department of Pediatrics, Yokohama City University, Japan

¹Correspondence: Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. E-mail: masafumi{at}kumamoto-u.ac.jp

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-. These results together indicate that the expression of CXCR3 is up-regulated 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.

Key Words: chemokine receptor • differentiation • cytokine

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