Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection.

Journal article

While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control. These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.

Authors: de Silva, T; Peng, Y; Leligdowicz, A; Zaidi, I; Li, L

• Publication status: Published
• Journal: Blood
• Volume: 121
• Issue: 21
• Pages: 4330-4339
• Publication date: 2013-05-01
• DOI: 10.1182/blood-2012-12-472787
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: GPI-Linked Proteins; Male; Humans; gag Gene Products, Human Immunodeficiency Virus; Flow Cytometry; Cell Proliferation; Aged, 80 and over; Aged; Female; Antigens, CD; Cell Differentiation; Programmed Cell Death 1 Receptor; Viremia; CD8-Positive T-Lymphocytes; Anti-Retroviral Agents; Middle Aged; HIV-2; Adult; Immunophenotyping; HIV Infections; Receptors, Immunologic