Editors' ChoiceIMMUNITY

The Lymphocyte Subset Club: New Members Welcome

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Science Translational Medicine  09 May 2012:
Vol. 4, Issue 133, pp. 133ec83
DOI: 10.1126/scitranslmed.3004257

Infections by fungus and antibiotic-resistant bacteria cause diseases that sometimes result in the development of life-threatening syndromes, such as sepsis. In humans, the dysfunction of T helper cell 17 (TH17) lymphocytes confers susceptibility to bacterial and fungal pathogens such as Staphylococcus aureus and Candida albicans, respectively. However, how TH17 lymphocytes defend against divergent microbes from different kingdoms is unclear. Now, new research by Zielinski et al. reveals that pathogen-specific TH17 subsets exist to deal with different microbial invaders.

The authors stimulated human T cells with pathogen-pulsed antigen-presenting cells and found that S. aureus–primed TH17 cells differed from C. albicans–primed TH17 cells. Specifically, fungus-primed, but not bacteria-primed, T cells produced interferon-γ (IFN-γ). Additionally, only S. aureus–stimulated TH17 cells developed the capacity to generate interleukin-10 (IL-10), and ex vivo restimulation of human memory T cells highlighted the pathogen-specific dichotomy of TH17 cells. Pathogen specificity was restricted by the absolute requirement of IL-1β for generating Candida-TH17 cells and suppression of IL-10 production. Moreover, TH17 cells demonstrated plasticity, as IL-1β could suppress IL-10 in previously differentiated in vivo memory T cells. Interestingly, in humans suffering from excessively high levels of IL-1β, memory T cells produced low levels of IL-10. However, after treatment with a pharmaceutical inhibitor of the IL-1 receptor, memory T cells regained the ability to generate IL-10, thus confirming the importance of IL-1β in regulating pathogen-specific TH17 and demonstrating effector lymphocyte plasticity.

The results of this study provide direct evidence for the existence of pathogen-specific human TH17 cells and further define two previously unidentified effector T cell subpopulations, which lead the authors to introduce the concept of “inflammatory” TH17 cells. This report demonstrates that differentiated memory T cells have significant plasticity and that using immune-modulators such as IL-1 blockers can alter previously differentiated TH17 cells. This observation opens up the possibility of manipulating the microbial specificity of in vivo T lymphocytes by modifying cytokine profiles.

C. E. Zielinski et al., Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 484, 514–518 (2012). [Abstract]

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