Circulating natural killer and gammadelta T cells decrease soon after infection of rhesus macaques with lymphocytic...

Area of Science:

• Immunology
• Virology
• Primate Models

Background:

• Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV-WE) model human Lassa fever virus infection.
• Understanding early immune events in acute viral infections is crucial.

Purpose of the Study:

• To identify the earliest changes in peripheral blood mononuclear cells (PBMCs) during acute LCMV-WE infection in rhesus macaques.
• To investigate the specific immune cell subsets affected during the early stages of infection.

Main Methods:

• Monitoring rhesus macaques immediately following lethal LCMV-WE infection.
• Analyzing changes in CD3, CD4, CD8, CD20, NK, and gammadelta T cell subsets in PBMCs.
• Conducting in vitro cell culture experiments with LCMV and specific T cell subsets.

Main Results:

• CD3, CD4, CD8, and CD20 cell populations showed normal fluctuations.
• Natural killer (NK) and gammadelta T cells increased on day 1, then significantly decreased by day 2.
• The decrease in NK cells involved CD3-CD8+ and CD3-CD16+ subsets, not NKT cells.
• In vitro studies showed apoptosis in V(3)9 T cells but insufficient NK cell death to explain the observed decrease.
• Similar decreases in NK and gammadelta T cells were observed in macaques infected with a non-virulent arenavirus, suggesting a non-pathogenic event.

Conclusions:

• The disappearance of circulating NK and gammadelta T cells during acute LCMV-WE infection in rhesus macaques is not solely due to direct viral pathogenesis.
• This phenomenon mirrors observations in LCMV-infected mice, where decreased NK cells were linked to margination and cell death.
• The observed lymphopenia is likely a cytokine-induced response, a common feature across various viral infections.