Down‐regulation of CXCR4 expression on human CD8⁺ T cells during peripheral differentiation

Abstract

Multi-color flow cytometric analysis on human CD8 + T cell subsets revealed that CXCR4 is predominantly expressed on CD8 + T cells with the naive CD27 + CD28 + CD45RA + phenotype, and is down-regulated during differentiation into those with an effector phenotype. The downregulation of CXCR4 expression during peripheral differentiation was supported by the fact that the expression of CXCR4 on CD8 + T cells was negatively correlated with that of perforin. The analysis of CCR5, CCR7, and CXCR4 co-expression further showed that CD8 + T cells expressing a high level of CXCR4 are CCR7 + CCR5 -naive or central memory subsets, and those expressing a low level of CXCR4 were included in the CCR7 -CCR5 +/-memory/effector and effector subsets. Epstein Barr virus-specific CD8 + T cells, which mostly express the memory phenotype, expressed CXCR4, while human cytomegalovirus-specific CD8 + T cells, which mostly express the effector phenotype, partially expressed this receptor, showing that the expression of CXCR4 is also down-regulated during differentiation of viral antigenspecific CD8 + T cells. The classification of human CD8 + T cells based on the expression of these chemokine receptors should prove useful for studies that clarify the differentiation of human CD8 + T cells.

CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis

“…Decreased responsiveness to CXCL12 and surface expression of CXCR4 occurs during the evolution of antiviral immune responses, allowing proper egress of leukocytes that participate in pathogen clearance (31). Consistent with these findings, we did not see alterations in T cell trafficking, virus-specific immune responses, or viral clearance within the spleens of WNV-infected mice treated with AMD3100, compared with similarly infected, vehicle-treated animals.…”

Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4 + T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells

“…In addition, loss of IL-2-producing T cells is a characteristic of exhaustion during HIV infection (26,39). Patients that receive IL-2 therapy in conjunction with HAART not only have slightly increased numbers of CD4 ϩ T cells but also exhibit an increase in the number of HIV-suppressive noncytolytic CD8 ϩ T cells (13,27,28,39 (28,31,49). The up-regulation of CXCR4 on intestinal CD8 ϩ T cells in PSI animals is additional evidence for less cytotoxic SIV-specific CD8 ϩ T cells (31,48,63).…”

Human Papillomavirus: Biology and Pathogenesis

“…T-cell response to E2 and E6 are lost or reduced in CIN 3 and carcinoma invasive. Thus, even if HPV antigen-specific cytotoxic Tcells have been generated, regulatory T-cells increasingly dominate the lesion and abrogate the killer defense response (Kobayashi et al, 2004). High-risk HPV infected cervical keratinocytes expressing high level risk of E6 and E7 oncoproteins are not killed in this immunosuppressive tolerante mileu, nad progression to high-grade disease and cancer can result (Stanley, 2009b).…”