Related Experiment Videos
Monocyte/macrophage giant cell disease in SIV-infected cynomolgus monkeys
S L Li1, E E Kaaya, H Feichtinger
1Immunopathology Lab., Karolinska Institute, Stockholm, Sweden.
Abstract:
A non-opportunistic, generalized giant cell disease (GCD) was found in 12 out of 25 (48%) cynomologus monkeys infected with SIVsm. Most organs were affected notably the lymph nodes (LN), spleen, gut, liver, lungs and CNS. The multinucleated GC varied considerably in cell size and in the number and cytoplasmic distribution of the nuclei. Immunohistochemically most GC expressed SIV antigens and markers of mononuclear phagocytes (CD68), CD4 and also occasionally the T-cell markers CD45RO, CD43 and CD2. Monkeys with GCD had more pronounced immunosuppression with lower CD4-cell counts, more often demonstrable SIV antigen in the blood and LN and had been infected for a longer time period, as compared to monkeys without GCD. These findings show that SIV infection in cynomolgus monkeys is frequently associated with extensive formation of multinucleated GC of macrophage origin, which appears to be related to the pathogenesis of the infection and the degree of immunosuppression.
Insights
Giant cell disease (GCD) in cynomolgus monkeys infected with SIVsm is common, affecting multiple organs. This condition correlates with increased immunosuppression and viral load, suggesting a role in SIV pathogenesis.
Area of Science:
- Veterinary Pathology
- Immunology
- Primate Virology
Background:
- Simian immunodeficiency virus (SIVsm) infection in non-human primates serves as a model for Human Immunodeficiency Virus (HIV) research.
- Giant cell disease (GCD) is a pathological finding characterized by multinucleated giant cells.
- The pathogenesis and full spectrum of SIVsm infection in cynomolgus monkeys are still under investigation.
Purpose of the Study:
- To investigate the occurrence and characteristics of GCD in SIVsm-infected cynomolgus monkeys.
- To determine the association between GCD and the degree of immunosuppression and viral burden.
- To elucidate the cellular origin and phenotype of the giant cells.
Main Methods:
- Necropsy and histopathological examination of 25 cynomolgus monkeys infected with SIVsm.
- Immunohistochemical analysis of giant cells for SIV antigens and cellular markers (CD68, CD4, CD45RO, CD43, CD2).
- Correlation of GCD presence with CD4+ T-cell counts, SIV antigenemia, and duration of infection.
Main Results:
- Generalized GCD was observed in 48% (12/25) of SIVsm-infected monkeys, affecting organs like lymph nodes, spleen, gut, liver, lungs, and CNS.
- Multinucleated giant cells expressed SIV antigens and mononuclear phagocyte markers (CD68), along with CD4 and occasionally T-cell markers.
- Monkeys with GCD exhibited more severe immunosuppression (lower CD4 counts), higher SIV antigen levels, and longer infection periods.
Conclusions:
- SIVsm infection frequently induces generalized GCD in cynomolgus monkeys.
- The giant cells are of macrophage origin and express viral antigens.
- GCD is associated with heightened immunosuppression and viral persistence, indicating its relevance to SIV pathogenesis.