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Updated: Jun 20, 2026
Multicolor Flow Cytometry Analyses of Cellular Immune Response in Rhesus Macaques
Published on: April 22, 2010
Circulating natural killer and gammadelta T cells decrease soon after infection of rhesus macaques with lymphocytic
Juan D Rodas1, Cristiana Cairo, Mahmoud Djavani
1Grupo de Investigaciones en Ciencias Veterinarias Centauro, Facultad de Ciencias Agrarias, Universidad de Antioquia, Medellín, Colombia.
Abstract:
Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs). Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK) and gammadelta T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3-CD8+ or CD3-CD16+ and not the NKT (primarily CD3+CD56+) subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and gammadelta T cells, indicating that this is not a pathogenic event. V(3)9 T cells, representing the majority of circulating gammadelta T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections.
Insights
Early viral hemorrhagic fever in rhesus macaques shows a decrease in natural killer (NK) and gammadelta T cells. This lymphopenia may be a common cytokine-induced response in many viral infections.
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.
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