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.
Rights and Permissions
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
DOI of Published Version
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.