Changes in function of HIV-specific T-cell responses with increasing time from infection

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Individuals with recent Human Immunodeficiency Virus (HIV) infection exhibit robust virus-specific T-cell responses, including interferon-gamma (IFN-γ)/interleukin-2 (IL-2) secretion and proliferation.
• These functional T-cell responses are often diminished in chronic HIV infection, suggesting a loss of immune function over time.

Purpose of the Study:

• To investigate the temporal dynamics of HIV-specific T-cell function loss in treatment-naïve individuals.
• To determine the time course of diminished T-cell responses, specifically IFN-γ/IL-2 secretion and proliferation, following HIV infection.

Main Methods:

• Screened peripheral blood mononuclear cells from 59 treatment-naïve HIV-infected individuals using ELISPOT assays to measure IFN-γ/IL-2 and IFN-γ secretion.
• Assessed HIV peptide-specific T-cell proliferation using carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution.
• Compared T-cell responses across different time intervals post-infection: <6 months, 6-12 months, and 12-36 months.

Main Results:

• The frequency of cells secreting both IFN-γ and IL-2 decreased over time post-infection.
• The frequency of cells secreting IFN-γ only increased with time from infection.
• HIV peptide-specific proliferative responses, predominantly mediated by CD8(+) T cells, were significantly lower in individuals infected 12-36 months prior compared to those infected <6 months prior.
• Significant differences in T-cell functions were observed by the second year of infection compared to the initial 6 months.

Conclusions:

• HIV-specific T-cell function, characterized by cytokine secretion and proliferation, declines significantly within the first two years of infection in treatment-naïve individuals.
• The loss of dual IFN-γ/IL-2 secretion and reduced proliferation indicate a progressive impairment of adaptive immunity during early HIV infection.