HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses

Area of Science:

• Immunology
• Infectious Diseases
• Public Health

Background:

• Human immunodeficiency virus (HIV) is a major risk factor for tuberculosis (TB) progression.
• HIV-infected individuals have an increased risk of developing TB, even when aviremic.
• This suggests factors beyond CD4 T-cell depletion contribute to TB susceptibility in HIV coinfection.

Purpose of the Study:

• To investigate the hypothesis that HIV impairs Mycobacterium tuberculosis (Mtb)-specific CD4 T-cell function.
• To compare T-cell responses and cytokine profiles in HIV-uninfected and HIV-coinfected individuals with latent TB infection (LTBI) or active pulmonary TB (PTB).
• To elucidate the impact of HIV on Mtb-specific immunity and systemic inflammation.

Main Methods:

• Analysis of Mtb-specific T-cell frequencies and cytokine production (Th2, IL-2) in Tanzanian LTBI and PTB patients.
• Comparison between HIV-uninfected and HIV-coinfected individuals.
• Assessment of PD-1 and Gata-3 expression on T cells and serum cytokine/chemokine levels (IL-1α, IL-6, CRP, IL-23, IP-10).

Main Results:

• HIV infection significantly reduced Mtb-specific CD4 T cells producing Th2 cytokines (IL-4, IL-5, IL-13) and IL-2.
• Loss of IL-2 production correlated with increased PD-1 expression, while loss of Th2 cytokines correlated with reduced Gata-3 expression.
• HIV-coinfected PTB patients showed reduced serum levels of proinflammatory cytokines (IL-1α, IL-6, CRP, IL-23, IP-10) compared to HIV-negative PTB patients.

Conclusions:

• HIV infection impairs functionally favorable Mtb-specific CD4 T-cell responses in individuals with LTBI and PTB.
• HIV diminishes Mtb-specific T-cell responses and suppresses Mtb-induced systemic proinflammatory cytokine responses.
• These functional impairments likely contribute to the increased susceptibility to TB disease in HIV-coinfected individuals.