Regulatory T Cells Resist Virus Infection-Induced Apoptosis

Regulatory T (Treg) cells are important in the maintenance of self-tolerance, and the depletion of Treg cells correlates with auto-immune 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 muchmore 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 con-ventional 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 infectionmay explain the relatively low incidence of autoim-munemanifestations among infected patients. IMPORTANCE Autoimmune diseases are controlled in part by regulatory T cells (Treg) and are thought to sometimes be initiated by viral infec-tions. We tested the hypothesis that Treg may die off at early stages of infection, when virus-induced factors kill other lympho-cyte types. Instead, we found that Treg resisted this cell death, perhaps reducing the tendency of viral infections to cause immune dysfunction and induce autoimmunity