The Development and Function of Memory Regulatory T Cells after Acute Viral Infections

Natural CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are critical for the control of immune responses to pathogens. However, most studies have focused on chronic infections, in which pathogen-specific Tregs contribute to pathogen persistence and, in some cases, concomitant immunity. How Tregs behave and function following acute infections remains largely unknown. In this article, we show that pathogen-specific Tregs can be activated and expand upon acute viral infections in vivo. The activated Tregs then contract to form a memory pool after resolution of the infection. These memory Tregs expand rapidly upon a secondary challenge, secrete large amounts of IL-10, and suppress excessive immunopathological conditions elicited by recall expansion of non-Tregs via an IL-10-dependent mechanism. Our work reveals a memory Treg population that develops after acute viral infections and may help in the design of effective strategies to circumvent excessive immunopathological effects. The Journal of Immunology, 2012, 189: 2805-2814.