HIV-1 Coreceptor CXCR4 Antagonists Promote Clonal Expansion of Viral Epitope-Specific CD8+ T Cells During Acute SIV Infection in Rhesus Monkeys In Vivo
| Autor: | Pijin Wei, Junli Huang, Zhenyou Jiang, Hanxiao Sun, Zhaobing Liu, Li Shiyu, Yahui Gong, Hailang Yu, Yan Yang, Qing Ding |
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| Rok vydání: | 2015 |
| Předmět: |
Receptors
CXCR4 Receptors CCR5 viruses T-cell receptor Simian Acquired Immunodeficiency Syndrome Epitopes T-Lymphocyte virus diseases CCR5 receptor antagonist CD8-Positive T-Lymphocytes Biology Simian immunodeficiency virus medicine.disease_cause Macaca mulatta Virology Epitope Chemokine receptor Infectious Diseases Immune system Immunology medicine Animals Cytotoxic T cell Simian Immunodeficiency Virus Pharmacology (medical) CD8 |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 69:145-153 |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/qai.0000000000000586 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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