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A ten-acious cytokine for a tenacious infection

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Science Immunology  01 Feb 2019:
Vol. 4, Issue 32, eaaw7720
DOI: 10.1126/sciimmunol.aaw7720

Abstract

T follicular helper cells produce interleukin-10 during chronic viral infections to support the humoral response.

T follicular helper (TFH) cells are now well appreciated for their role in promoting high affinity, long-lived antibody responses. Interleukin-21 (IL-21) and IL-4 are important TFH cell–derived cytokines, supporting germinal center (GC) B cell survival. TFH cells have additionally been found to produce a range of effector cytokines—including interferon-γ (IFN-γ), IL-4, IL-9, and IL-17—for directing immunoglobulin isotype switching and B cell differentiation appropriate to a given immune response. IL-10 is an unexpected cytokine that has been added to the list, specifically during chronic viral infections. Though better known for its immunosuppressive properties, IL-10 has recently been shown to promote the GC response when produced by T follicular regulatory (TFR) cells in the context of acute viral infection. Now Xin et al. demonstrate that IL-10 derived from TFH cells, transcriptionally distinct from TFR cells, is critical for protective humoral immunity during chronic viral infection. Using a model of lymphocytic choriomeningitis virus (LCMV) infection, the authors identify a population of IL-10+IL-21+ coproducing TFH cells induced during chronic—but not acute—infection. Further, these cells are induced but not sustained in more prolonged influenza infection. Specific depletion of IL-10+IL-21+ TFH cells reduces LCMV-specific antibody titers. IL-10 is the operative signal produced by these TFH cells, as evinced by the impaired humoral responses in mice with either TFH cell–specific loss of IL-10 or B cell–specific loss of the IL-10 receptor. Taken together, Xin et al. add IL-10 to the ever-growing list of TFH cell effector cytokines, helping to better define how TFH cells regulate the humoral response in various immune contexts. It will be interesting to compare the nature and function of these IL-10–producing TFH cells with a recently described IL-10–producing non-TFH cell population shown to support B cell activation in patients with the chronic autoimmune disease lupus (Caielli et al. Nat. Med. 2019). Although additional mechanistic studies are required to clarify the role of this cytokine for B cell responses, such studies shed light on how the immune system is exquisitely tailored to respond to a variety of immunologic targets.

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