Thursday, January 05, 2012

Foxp3(+) Regulatory T cells, Immune Stimulation and Host Defense against Infection

Immunology. 2011 Dec 29. doi: 10.1111/j.1365-2567.2011.03551.x. [Epub ahead of print]

Foxp3(+) Regulatory T cells, Immune Stimulation and Host Defense against Infection.

Rowe JH, Ertelt JM, Way SS.

Departments of Pediatrics and Microbiology University of Minnesota School of Medicine Center for Infectious Disease and Microbiology Translational Research.

The immune system is intricately regulated allowing potent effectors to expand and become rapidly mobilized after infection, while simultaneously silencing potentially detrimental responses that averts immune-mediated damage to host tissues. This relies in large part on the delicate interplay between immune suppressive regulatory CD4(+) T cells (Tregs) and immune effectors that without active suppression by Tregs cause systemic and organ-specific autoimmunity. Although these beneficial roles have been classically described to be counter-balanced by impaired host defense against infection, newfound protective roles for Tregs against specific viral pathogens (e.g. Herpes simplex-2, Lymphocytic choriomeningitis, West Nile virus) have been uncovered using transgenic mice that allow in vivo Treg-ablation based on Foxp3-expression. In turn, Foxp3(+) Tregs also provide protection against some parasitic (Plasmodium sp., Toxoplasma gondii) and fungal (Candida albicans) pathogens. By contrast for bacterial and mycobacterial infections (e.g. Listeria monocytogenes, Salmonella enterica, Mycobacterium tuberculosis), experimental manipulation of Foxp3(+) cells continue to indicate detrimental roles for Tregs in host defense. This discordance is likely related to functional plasticity in Treg suppression that shifts discordantly following infection with different types of pathogens. Furthermore, the efficiency whereby Tregs silence immune activation coupled with the plasticity in Foxp3(+) cell activity suggest overriding Treg-mediated suppression represents a prerequisite "signal zero" that together with other stimulation signals (T cell receptor [signal 1], co-stimulation [signal 2], inflammatory cytokines [signal 3]) are essential for T cell activation in vivo. Herein, the importance of Foxp3(+) Tregs in host defense against infection, and the significance of infection-induced shifts Treg suppression are summarized.

Journal compilation © 2011 Blackwell Publishing Ltd.

PMID: 22211994 [PubMed - as supplied by publisher]

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