Regulatory T Cells in Infection

Maizels, Rick M.; Smith, Katherine A.

Infectious agents have intimately co-evolved with the host immune system, acquiring a portfolio of highly sophisticated mechanisms to modulate immunity. Among the common strategies developed by viruses, bacteria, protozoa, helminths, and fungi is the manipulation of the regulatory T cell network in order to favor pathogen survival and transmission. Treg activity also benefits the host in many circumstances by controlling immunopathogenic reactions to infection. Interestingly, some pathogens are able to directly induce the conversion of naive T cells into suppressive Foxp3-expressing Tregs, while others activate pre-existing natural Tregs, in both cases repressing pathogen-specific effector responses. However, Tregs can also act to promote immunity in certain settings, such as in initial stages of infection when effector cells must access the site of infection, and subsequently in ensuring generation of effector memory. Notably, there is little current information on whether infections selectively drive pathogen-specific Tregs, and if so whether these cells are also reactive to self-antigens. Further analysis of specificity, together with a clearer picture of the relative dynamics of Treg subsets over the course of disease, should lead to rational strategies for immune intervention to optimize immunity and eliminate infection.