T cell responses

Autocrine transforming growth factor-β1 promotes in vivo Th17 cell differentiationGutcher, I. et al. Immunity 34, 396–408 (2011)

Foxp3+ regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2Chen, Y. et al. Immunity 34, 409–421 (2011)

CD4+CD25+Foxp3+ regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection modelPandiyan, P. et al. Immunity 34, 422–434 (2011)

Transforming growth factor-β (TGFβ) is secreted by regulatory T (TReg) cells and is thought to be important for promoting both the development and the anti-inflammatory functions of these cells. More recently, TFGβ was shown to be involved in the differentiation of pro-inflammatory T helper 17 (TH17) cells; this was somewhat counter-intuitive, as TReg cells can inhibit pro-inflammatory TH17 cell responses in mouse models of disease (such as experimental autoimmune encephalomyelitis (EAE)). Three studies in Immunity now add an additional layer of complexity to the story. By conditionally depleting TGFβ expression in TReg cells or in both TReg cells and effector T cells, Gutcher et al. showed that autocrine production of TGFβ by TH17 cells, rather than paracrine responsiveness to TReg cell-derived TGFβ, is required for TH17 cell differentiation and the development of EAE. Chen et al. came to a similar conclusion, showing that TH17 cells still develop normally when TReg cells are unable to express TGFβ. However, these authors found that conditional depletion of TReg cells did, in fact, inhibit TH17 cell development in vivo. This effect was shown to result from the loss of TReg cell-mediated consumption of interleukin-2 (IL-2), which inhibits TH17 cells. Pandiyan et al. echoed the findings of both studies, showing that IL-2 consumption by TReg cells, and not their ability to secrete TGFβ, allows this subset to promote TH17 cell development. Furthermore, they found that in mice infected with Candida albicans, TReg cell-mediated support of TH17 cell differentiation enhanced fungal clearance and recovery from infection. Pandiyan et al. suggest that TReg cells are not just important for suppressing immune responses — they can also contribute to protective immunity by supporting inflammatory TH17 cell responses during infection.

Vaccines

An inactivated cell-culture vaccine against yellow fever Monath, T. P. et al. N. Engl. J. Med. 364, 1326–1333 (2011)

Although there is a highly effective vaccine for yellow fever (a lethal viral disease spread by mosquitoes in the tropics), this live attenuated vaccine can have serious side effects. Thus, there is a need for a safer, non-replicating vaccine, particularly for immunocompromised individuals. The first Phase I study of such a vaccine in healthy humans has shown promising results. A single injection of a high dose of XRX-001 (which comprises whole inactivated virus adsorbed to aluminium hydroxide) induced the development of virus-specific neutralizing antibodies in 46% of the study group. Furthermore, following a booster injection of XRX-001, 100% of the subjects developed neutralizing antibodies. The next important issue to address is whether XRX-001 can induce long-lasting protective immunity against yellow fever, in a similar manner to the live attenuated vaccine.