CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+ T Cells

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-γ by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-γ production. The effect of CpG and IL-15 was also evident with CD8+ T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+ T cells and CD4+CD25+ regulatory T cells. Although IFN-γ was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+ T cells required expression of the IFN-γ-inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8+ T-cell responses to infectious agents and tumors

A Year in, Americans Still Support Ukraine

A majority of the US public continues to back current military and financial aid to Kyiv, recent polls find.The war in Ukraine is about to enter its second year, with rumors of a new Russian offensive being planned to mark the occasion. At the same time, US headlines have warned that some congressional support for US aid to Ukraine may be sliding, and several polls have shown that American public support for continuing to assist Ukraine "for as long as it takes" has slipped from the very high levels seen at the outset of the conflict. But these analyses often overlook the fact that Americans are still paying attention to the conflict one year into it, and their support for current military and financial aid to Kyiv remains at majority levels

Americans Support Ukraine--but Not with US Troops or a No-Fly Zone

A new poll reveals that Americans see Russia as a significant threat to US interests and support military and economic assistance to Ukraine.In response to Russia's aggression toward Ukraine, the United States and its allies have imposed sanctions on Russia that are striking in their scope and severity and represent a broad effort to impose serious economic costs on Russia for its invasion of Ukraine. For their part, a March 25-28 Chicago Council survey finds that Americans support all measures to help Ukraine and pressure Russia short of direct US involvement in a military conflict. And while the public views the broad sanctions imposed on Russia as generally effective at punishing, weakening, and deterring Russia from further aggression, they doubt that sanctions will be enough to persuade Moscow to withdraw troops from Ukraine—the key condition Americans identify as necessary for lifting sanctions

CpG and Interleukin-15 Synergize to Enhance IFN-gamma Production by Activated CD8(+) T Cells

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells. Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-gamma by CD8(+) T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-gamma production. The effect of CpG and IL-15 was also evident with CD8(+) T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8(+) T cells and CD4(+)CD25(+) regulatory T cells. Although IFN-gamma was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8(+) T cells required expression of the IFN-gamma-inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8(+) T-cell responses to infectious agents and tumors

CpG and Interleukin-15 Synergize to Enhance IFN- Production by Activated CD8+ T Cells

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8+ T cells. Paradoxically, we previously reported that IL-15 could enhance CD8+ T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8+ T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN- by CD8+ T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN- production. The effect of CpG and IL-15 was also evident with CD8+ T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8+ T cells and CD4+CD25+ regulatory T cells. Although IFN- was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8+ T cells required expression of the IFN--inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8+ T-cell responses to infectious agents and tumors

Russians and Americans Sense a New Cold War

The current conflict in Ukraine is described by some as an inflection point in world history, and perhaps the end of the post-Cold War era. Russian President Vladimir Putin increasingly seems to make foreign policy decisions designed to upend the US-European security order and dominate the countries he considers to be in Russia's orbit. At the same time, US President Joe Biden has pitted the NATO struggle with Russia as well as the US competition with China as contests between democracies and autocracies. A recent public opinion survey from the Chicago Council on Global Affairs and the Levada Center in Moscow shows that Russians and Americans view global divisions along Cold War lines. And in what may be the most alarming throwback to those days, large majorities in both countries fear an escalation to nuclear war

IL-15/IL-15Rα Heterodimeric Complex as Cancer Immunotherapy In Murine Breast Cancer Models

Interleukin 15 (IL-15) has been evaluated as a potential treatment for solid tumors in clinical trials, but the effectiveness of systemic IL-15 administration as a monotherapy has not been realized. IL-15 receptor alpha (IL-15Rα) can stabilize IL-15 and enhance its bioactivity. The goal of this study was to examine the activity of IL-15/IL-15Rα complex (IL-15cx) to CD8(+) T cells and evaluate its potential efficacy in murine breast cancer models. The antitumor efficacy was studied in mouse mammary carcinoma models (Her2/neu transgenic and 4T1-luc mammary cancers) treated with systemic recombinant protein with/without the depletion of myeloid-derived suppressor cells or intra-tumoral gene electrotransfer (GET). IL-15cx shows superior in vivo bioactivity to expand CD8 T cells in comparison to an equimolar single chain IL-15. T-bet is partially involved in CD8 T cell expansion ex vivo and in vivo due to IL-15 or IL-15cx. Intraperitoneal administration of IL-15cx results in a moderate inhibition of breast cancer growth that is associated with an increase in the frequency of cytotoxic CD8 T cells and the improvement of their function. The depletion of myeloid-derived suppressor cells (MDSCs) has no impact on mouse breast cancer growth. IL-15cx treatment diminishes MDSCs in murine tumors. However, it also antagonizes the effects of anti-Gr-1 depleting antibodies. Intratumoral GET with plasmid IL-15/IL-15Rα leads to a long-term survival benefit in 4T1 mammary carcinoma model. An early increase of local cytotoxic cells correlates with GET treatment and an increase of long-term memory T cells results from animals with complete tumor regression. Systemic and local administration of IL-15cx shows two distinct therapeutic responses, a moderate tumor growth inhibition or heterogeneous tumor regressions with survival improvement. Further studies are warranted to improve the efficacy of IL-15cx as an immunotherapy for breast cancer

Russian Public Accepts Putin's Spin on Ukraine Conflict

A new Chicago Council-Levada poll reveals the Russian public appears to be buying Putin's explanation for "military operation" in Ukraine.While the whole world seems to be watching the Russian "special military operation" in Ukraine, a new joint survey by the Chicago Council on Global Affairs and the Levada Center conducted March 24–30 shows that most people living in Russia are not following these events closely. Nevertheless, a majority of Russians say they support their country's military action—with just over half strongly backing it. For the most part, Russians think these actions are being taken to protect and defend fellow Russians and Russian speakers in Ukraine, to protect Russia itself, or to "denazify" Ukraine—storylines that have been amplified by the Russian government's media apparatus. But as the conflict drags on, it may become more difficult to sustain this support, especially as the casualty rates are uncovered and the economic repercussions of the Western sanctions begin to more seriously affect Russian households

Race, Ethnicity, and American Views of Climate Change

Asian, Hispanic, and Black Americans are more likely to view climate change as a threat than Americans as a whole, data show.In the United States, definitions of national security threats are shifting, highly politicized, and closely tied to identity. At the same time, the US is more racially diverse than at any time in its past. To better understand how this diversity feeds into threat perception, the Chicago Council on Global Affairs and the New America Foundation have partnered to conduct novel research on the views of white, Black, Asian, Hispanic, and Native Americans as part of the 2022 Chicago Council Survey