Immunology & Microbiology
Department of Pathology
Medical Subject Headings
Animals; *Apoptosis; Arenaviridae Infections; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Survival; Gene Expression Regulation; Interferon Type I; Interleukin-7; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; T-Lymphocytes, Regulatory
Allergy and Immunology | Immunology and Infectious Disease | Immunology of Infectious Disease | Immunopathology | Microbiology | Virology | Virus Diseases
Regulatory T (Treg) cells are important in the maintenance of self-tolerance, and the depletion of Treg cells correlates with autoimmune development. It has been shown that type I interferon (IFN) responses induced early in the infection of mice can drive memory (CD44hi) CD8 and CD4 T cells into apoptosis, and we questioned here whether the apoptosis of CD44-expressing Treg cells might be involved in the infection-associated autoimmune development. Instead, we found that Treg cells were much more resistant to apoptosis than CD44hi CD8 and CD4 T cells at days 2 to 3 after lymphocytic choriomeningitis virus infection, when type I IFN levels are high. The infection caused a downregulation of the interleukin-7 (IL-7) receptor, needed for survival of conventional T cells, while increasing on Treg cells the expression of the high-affinity IL-2 receptor, needed for STAT5-dependent survival of Treg cells. The stably maintained Treg cells early during infection may explain the relatively low incidence of autoimmune manifestations among infected patients.
IMPORTANCE: Autoimmune diseases are controlled in part by regulatory T cells (Treg) and are thought to sometimes be initiated by viral infections. We tested the hypothesis that Treg may die off at early stages of infection, when virus-induced factors kill other lymphocyte types. Instead, we found that Treg resisted this cell death, perhaps reducing the tendency of viral infections to cause immune dysfunction and induce autoimmunity.
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Citation: J Virol. 2015 Feb;89(4):2112-20. doi: 10.1128/JVI.02245-14. Epub 2014 Dec 3. Link to article on publisher's site
Journal of virology
Che, Jenny Wun-Yue; Kraft, Anke R.M.; Selin, Liisa K.; and Welsh, Raymond M., "Regulatory T cells resist virus infection-induced apoptosis" (2015). GSBS Student Publications. 1937.