Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells

PLoS Pathogens

Virginie Rozot¹  Felicitas Bellutti Enders¹  Cristina Cellerai¹  Matthieu Perreau¹  Selena Viganò¹  Anne-Laure Savoye¹  Giuseppe Pantaleo¹  Alexandre Harari¹  Isabelle Miconnet¹  Khalid Ohmiti¹  Pierre-Alexandre Bart²  Mohamed Faouzi³  Matthias Cavassini³ 

[1] Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland;Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland;The Center of Clinical Epidemiology, Institut de Médecine Sociale et Préventive, Lausanne University Hospital, Lausanne, Switzerland

关键词: T cells;    Cytotoxic T cells;    HIV infections;    Viremia;    Antiretroviral therapy;    Cloning;    Flow cytometry;    Viral replication;   

DOI  :  10.1371/journal.ppat.1003423

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.

【 授权许可】

CC BY