CXCR3 Expression Elevated on Peripheral CD8(+) Lymphocytes from HIV/HCV Coinfected Individuals.

Abstract

HIV/HCV coinfected patients tend to develop hepatitis C (HCV)-associated liver disorders. Because the chemokine receptor CXCR3 participates in lymphocyte trafficking during hepatic inflammation, it may participate in the escalated liver disorders of coinfected patients. However, to date, the relative frequency and density of receptor on lymphocytes has not been established. This study compared the CXCR3(+) phenotype under various in vitro conditions between lymphocytes from healthy and coinfected individuals. Peripheral lymphocytes were stimulated with phytohemagluttinin for 0-7 d and phenotypes were determined by flow cytometry. Secreted cytokines were measured in culture supernatants by ELISA. Phenotypic differences were observed between groups. CD4(+)CXCR3(+) frequency between groups was equivalent before and during early activation, but increased only among non-infected individuals during late activation (p<0.001). In contrast, CD8(+)CXCR3(+) frequency was consistently greater (p<0.05) among HIV/HCV patients throughout activation. Among those who were non-infected, CD8(+)CXCR3(+) frequency increased (p=0.002) during late activation. However, CD8(+)CXCR3(+) frequency among HIV/HCV patients increased within 24 h of activation (p=0.008), and was nearly universal by late activation (p<0.001). Both groups elaborated Th-1 cytokine profiles; however, coinfected patients released more inflammatory cytokines (p<0.01) than non-infected individuals. In summary, we demonstrated that CD8(+) lymphocytes from HIV/HCV-infected patients expressed more CXCR3 and showed greater upregulatory ability upon activation. The atypical CXCR3 expression and enhanced Th-1 cytokine elaboration among coinfected patients could potentially stimulate increased lymphocyte migration during hepatic inflammation.

• Authors: Pam Kimball, Felecia McDougan, Richard Stirling
• Journal: Viral immunology (Viral Immunol) Vol. 24 Issue 6 Pg. 441-8 (Dec 2011) ISSN: 1557-8976 [Electronic] United States
• PMID: 22111598 (Publication Type: Journal Article)

Chemical References

• CXCL10 protein, human
• CXCR3 protein, human
• Chemokine CXCL10
• Culture Media
• Cytokines
• Phytohemagglutinins
• RNA, Viral
• Receptors, CXCR3

Topics

• CD8-Positive T-Lymphocytes (drug effects, immunology, metabolism, virology)
• Case-Control Studies
• Cell Proliferation
• Cells, Cultured
• Chemokine CXCL10 (metabolism, pharmacology)
• Coinfection (complications, immunology, virology)
• Culture Media (metabolism)
• Cytokines (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• HIV (immunology, pathogenicity)
• HIV Infections (complications, immunology, virology)
• Hepacivirus (immunology, pathogenicity)
• Hepatitis C (complications, immunology, virology)
• Humans
• Male
• Middle Aged
• Phenotype
• Phytohemagglutinins (pharmacology)
• RNA, Viral (genetics)
• Receptors, CXCR3 (immunology)
• Time Factors