RESEARCH HIGHLIGHTS Nature Reviews Immunology | AOP, published online 7 April 2014; doi:10.1038/nri3662
R E G U L AT O RY T C E L L S
Promoting B cell responses to influenza virus CD4+ T follicular helper (TFH) cells promote the formation of germinal centres (GCs) and support the differ entiation of antigen-specific B cells into memory B cells and plasma cells; processes that are inhibited by interleukin‑2 (IL‑2). Now, León et al. show that forkhead box P3 (FOXP3)expressing regulatory T (TReg) cells control the availability of IL‑2 and thereby promote antigen-specific B cell and TFH cell responses to influenza virus. TReg cells are generally defined by their ability to suppress immune cell responses but a few studies have indicated that TReg cells may promote antigen-specific B cell responses under certain circumstances by mechanisms that are incompletely understood. To investigate whether TReg cells influence the GC B cell response, the authors intranasally infected wildtype and TReg cell-depleted mice with influenza virus. They found that mice lacking TReg cells showed a decreased frequency of GC B cells that were specific for influenza virus, suggesting that TReg cells promote the generation of these cells.
the frequency of influenza virus-specific TFH cells was decreased in mice that lacked TReg cells
Next, the authors investigated whether TReg cells can inhibit the TFH cell response to infection with influenza virus and they found that the frequency of influenza virusspecific TFH cells was decreased in mice that lacked TReg cells com pared with control animals. Thus, FOXP3+ TReg cells promote, rather than inhibit, the influenza virusspecific TFH cell response. Of note, the authors found that the virus-specific TFH cells were not derived from FOXP3+CD4+ T cell precursors, as it was shown that FOXP3 was never expressed by the virus‑specific T cells. How could TReg cells regulate the TFH cell response to influenza virus? As TReg cells compete with other T cells for IL‑2, and thereby regulate T cell responses by influencing IL‑2 availability, the authors hypothesized that the absence of TReg cells could result in an excess of IL‑2 that could in turn prevent the differentia tion of TFH cells.
To investigate this, they determined the frequency of IL‑2‑producing CD4+ T cells in wild-type mice and TReg cell-depleted mice that were infected with influenza virus. Indeed, the number of IL‑2‑producing CD4+ T cells was increased in mice that lacked TReg cells compared with control mice. Furthermore, they found that the loss of TReg cells was associated with increased IL‑2 receptor signalling, which prevented the expression of the transcriptional regulator B cell lymphoma 6 (BCL‑6) and the development of influenza virus‑specific TFH cells. Taken together, this study dem onstrates a non-suppressive role of FOXP3+ TReg cells in the development of TFH cells in the context of influenza virus infection. The authors speculate that the ability of TReg cells to promote TFH cell and GC B cell responses via IL‑2 may depend on both the type of immune challenge and the location of the TReg cells. Elisabeth Kugelberg
ORIGINAL RESEARCH PAPER León, B. et al. FoxP3+ regulatory T cells promote influenzaspecific TFH responses by controlling IL‑2 availability. Nature Commun. 5, 3495 (2014)
r/Alamy Daniel Kaesle
NATURE REVIEWS | IMMUNOLOGY
VOLUME 14 | MAY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
R E G U L AT O RY T C E L L S
Promoting B cell responses to influenza virus CD4+ T follicular helper (TFH) cells promote the formation of germinal centres (GCs) and support the differ entiation of antigen-specific B cells into memory B cells and plasma cells; processes that are inhibited by interleukin‑2 (IL‑2). Now, León et al. show that forkhead box P3 (FOXP3)expressing regulatory T (TReg) cells control the availability of IL‑2 and thereby promote antigen-specific B cell and TFH cell responses to influenza virus. TReg cells are generally defined by their ability to suppress immune cell responses but a few studies have indicated that TReg cells may promote antigen-specific B cell responses under certain circumstances by mechanisms that are incompletely understood. To investigate whether TReg cells influence the GC B cell response, the authors intranasally infected wildtype and TReg cell-depleted mice with influenza virus. They found that mice lacking TReg cells showed a decreased frequency of GC B cells that were specific for influenza virus, suggesting that TReg cells promote the generation of these cells.
the frequency of influenza virus-specific TFH cells was decreased in mice that lacked TReg cells
Next, the authors investigated whether TReg cells can inhibit the TFH cell response to infection with influenza virus and they found that the frequency of influenza virusspecific TFH cells was decreased in mice that lacked TReg cells com pared with control animals. Thus, FOXP3+ TReg cells promote, rather than inhibit, the influenza virusspecific TFH cell response. Of note, the authors found that the virus-specific TFH cells were not derived from FOXP3+CD4+ T cell precursors, as it was shown that FOXP3 was never expressed by the virus‑specific T cells. How could TReg cells regulate the TFH cell response to influenza virus? As TReg cells compete with other T cells for IL‑2, and thereby regulate T cell responses by influencing IL‑2 availability, the authors hypothesized that the absence of TReg cells could result in an excess of IL‑2 that could in turn prevent the differentia tion of TFH cells.
To investigate this, they determined the frequency of IL‑2‑producing CD4+ T cells in wild-type mice and TReg cell-depleted mice that were infected with influenza virus. Indeed, the number of IL‑2‑producing CD4+ T cells was increased in mice that lacked TReg cells compared with control mice. Furthermore, they found that the loss of TReg cells was associated with increased IL‑2 receptor signalling, which prevented the expression of the transcriptional regulator B cell lymphoma 6 (BCL‑6) and the development of influenza virus‑specific TFH cells. Taken together, this study dem onstrates a non-suppressive role of FOXP3+ TReg cells in the development of TFH cells in the context of influenza virus infection. The authors speculate that the ability of TReg cells to promote TFH cell and GC B cell responses via IL‑2 may depend on both the type of immune challenge and the location of the TReg cells. Elisabeth Kugelberg
ORIGINAL RESEARCH PAPER León, B. et al. FoxP3+ regulatory T cells promote influenzaspecific TFH responses by controlling IL‑2 availability. Nature Commun. 5, 3495 (2014)
r/Alamy Daniel Kaesle
NATURE REVIEWS | IMMUNOLOGY
VOLUME 14 | MAY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
