title: HIV-1 Coreceptor CXCR4 Antagonists Promote Clonal Expansion of Viral Epitope-Specific CD8+ T Cells During Acute SIV Infection in Rhesus Monkeys In Vivo.
abstract: BACKGROUND
  The underlying molecular mechanisms and the kinetics of T cell receptor (TCR) repertoire selection during administration of CXCR4 or CCR5 inhibitors in infection of AIDS viruses in vivo have remained largely unexplored. Viral epitope-specific CD8(+) T lymphocytes play a dominant role in the control of HIV and simian immunodeficiency virus (SIV). We hypothesized that blockade of CXCR4 or CCR5 might influence the clonal expansion of epitope-specific CD8(+) T cells, contributing to antiviral immune responses in vivo.
  
  
  METHODS
  We measured frequencies of the dominant epitope p11C-specific CD8(+) T cells and analyzed the TCR repertoire of those cells in SIV-infected rhesus monkeys treated by CXCR4 or CCR5 inhibitors and vMIP-II, which binds multiple chemokine receptors.
  
  
  RESULTS
  A significantly increase in the levels of epitope-specific CD8(+) T cells was observed after blockade of CXCR4 or CCR5 compared with untreated control groups. Those CD8(+) T cells exhibited selected usage of TCR Vβ families and complementarity-determining region 3 (CDR3) segments. The clonal expansion of distinct Vβ populations could efficiently inhibit SIV replication in vitro, and CXCR4 inhibitor induced more expansion of epitope-specific CD8(+) T cells than CCR5 antagonist (P < 0.01), whereas vMIP-II treatment showed the most marked augmentation of p11C-specific CD8(+) T cells.
  
  
  CONCLUSIONS
  Antagonists of HIV coreceptors, particularly CXCR4, play an important role in the clonal expansion of SIV epitope-specific CD8(+) T cells in vivo, thus inhibitors of chemokine receptors such as CXCR4 or CCR5 may contribute to the ability of epitope-specific CD8(+) T cells to inhibit SIV or HIV infection.
authors.affiliation: *Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, China; †Institute of Genetic Engineering, Southern Medical University, Guangzhou, China; and ‡Departments of Microbiology and Immunology, Jinan University, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.forename: Shiyu
authors.initials: S
authors.lastname: Li
authors.forename: Zhenyou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Hailang
authors.initials: H
authors.lastname: Yu
authors.forename: Pijin
authors.initials: P
authors.lastname: Wei
authors.forename: Zhaobing
authors.initials: Z
authors.lastname: Liu
authors.forename: Junli
authors.initials: J
authors.lastname: Huang
authors.forename: Yahui
authors.initials: Y
authors.lastname: Gong
authors.forename: Hanxiao
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D008253:Macaca mulatta; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D019713:Receptors, CCR5; D019718:Receptors, CXCR4