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Regulatory T (T(reg)) cells are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage from immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. Here we show that T(reg) cells acquire an effector-like state, yet remain stable and functional, when exposed to interferon gamma (IFNγ) during infection with lymphocytic choriomeningitis and influenza A virus. T(reg) cell-restricted deletion of the IFNγ receptor (encoded by Ifngr1), but not the interleukin 12 (IL12) receptor (encoded by Il12rb2), prevented T(H)1-like polarization (decreased expression of T-bet, CXC motif chemokine receptor 3 and IFNγ) and promoted T(H)2-like polarization (increased expression of GATA-3, CCR4 and IL4). T(H)1-like T(reg) cells limited CD8(+) T cell effector function, proliferation and memory formation during acute and chronic infection. These findings provide fundamental insights into how T(reg) cells sense inflammatory cues from the environment (such as IFNγ) during viral infection to provide guidance to the effector immune response. This regulatory circuit prevents prolonged immunoinflammatory responses and shapes the quality and quantity of the memory T cell response.

Robust CD8+ T cell memory is essential for long-term protective immunity but is often compromised in cancer, where T cell exhaustion leads to loss of memory precursors. Immunotherapy via checkpoint blockade may not effectively reverse this defect, potentially underlying disease relapse. Here we report that mice with a CD8+ T cell–restricted neuropilin-1 (NRP1) deletion exhibited substantially enhanced protection from tumor rechallenge and sensitivity to anti-PD1 immunotherapy, despite unchanged primary tumor growth. Mechanistically, NRP1 cell-intrinsically limited the self-renewal of the CD44+PD1+TCF1+TIM3− progenitor exhausted T cells, which was associated with their reduced ability to induce c-Jun/AP-1 expression on T cell receptor restimulation, a mechanism that may contribute to terminal T cell exhaustion at the cost of memory differentiation in wild-type tumor-bearing hosts. These data indicate that blockade of NRP1, a unique ‘immune memory checkpoint’, may promote the development of long-lived tumor-specific Tmem that are essential for durable antitumor immunity. T cell exhaustion limits antitumor immune responses. Vignali and colleagues identify neuropilin-1 as a novel immune checkpoint that cell-intrinsically operates to limit memory cell formation and can be targeted to enhance antitumor responses.

From 1994 to 2003, fifty-five tropical cyclones entered the Canadian Hurricane Centre (CHC) Response Zone, or about 42% of all named Atlantic tropical cyclones in this ten-year period, and 2003 was the fourth consecutive year for a tropical cyclone to make landfall in Canada. The CHC forecasts all tropical cyclones that enter the CHC Response Zone and assumes the lead in forecasting once the cyclone enters its area of forecast responsibility. This study acknowledges the challenges of forecasting such tropical cyclones at extratropical latitudes. If a tropical cyclone has been declared extratropical, global models may no longer use vortex bogussing to carry the cyclone, and even if it is modeled, large model errors often result. The purpose of this study is to develop a new version of the Florida State University (FSU) hurricane superensemble with greater skill in tracking tropical cyclones, especially at extratropical latitudes. This has been achieved from the development of the synthetic superensemble, which is similar to the operational version of the multi-model superensemble that is used at FSU. The synthetic superensemble differs in that is has a larger set of member models consisting of regular member models, synthetic versions of these models, and the operational superensemble and its synthetic version. This synthetic superensemble is being used here to forecast hurricane tracks from the 2001, 2002, and 2003 hurricane seasons. The track forecasts from this method have generally less error than those of the member models, the operational superensemble, and the ensemble mean. This study shows that the synthetic superensemble performs consistently well and would be an asset to operational hurricane track forecasting.