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 (CXCR3high) and one expressing a low level of it (CXCR3low), but those with the effector phenotype (CD27- CD28- CD45RA+/-) included a population that did not express CXCR3 (CXCR3-) and a CXCR3low 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. CXCR3high 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, CXCR3high CD27+ CD28+ CD45RA- CD8+ T cells had the ability to produce interleukin-2 and interferon-gamma. These results together indicate that the expression of CXCR3 is up-regulated on intermediately differentiated memory CD8+ T cells. CXCR3high CD8+ T cells had a greater ability to migrate in response to CXCR3 ligands than CXCR3low ones. As CXCR3high 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.
Kobayashi
Naoki
N
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
Kondo
Takaaki
T
Takata
Hiroshi
H
Yokota
Shumpei
S
Takiguchi
Masafumi
M
D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis; D003587:Cytomegalovirus / Q000276:immunology; D005805:Genes, MHC Class I; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
C515370:CCR7 protein, human; D018106:CD28 Antigens; C515187:CXCR3 protein, human; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens