💡Exciting news! Our latest study, in collaboration with Prof. Mirela Kuka’s lab, is out now—uncovering how T cell–derived IFN-γ can suppress T follicular helper (TFH) cells and limit antibody responses. 🚀🧵(1/10) embopress.org/doi/full/10.10… 🔬Approach: We used a subcutaneous LCMV infection model, tracking virus-specific CD4⁺ T cells. Surprisingly, we found two T-bet⁺ subsets—one producing granzyme B (GzmB) and another expressing Tcf-1, the latter being a TFHprecursor. (2/10) 🌟Key Finding: IFN-γ from T cells drives the TH1 fate and blocks TFHmaturation. When we blocked IFN-γ early, Tcf-1⁺ “precursor” cells fully developed into TFH, boosting germinal center B cells and antibody responses. (3/10) 📊Mechanism: Rather than acting solely via an “autocrine loop,” IFN-γ shapes the microenvironment by acting on other immune cells—likely dendritic cells—thereby steering CD4⁺ T cells toward a TH1-dominant response at the expense of TFH. (4/10) 📌Infections & Vaccines: We also tested other settings—like systemic infections or even MPLA-based immunizations—and consistently observed that reducing IFN-γ can enhance TFH and humoral immunity. Timing is critical for optimal effect. (5/10) 🧬Broader Impact: Our data help explain why some infections trigger robust TH1activity but limited antibody responses, and highlight how precisely timed IFN-γ modulation could improve immunization strategies. (6/10) 🔑Clinical Relevance: In severe or chronic viral infections, TH1-skewed responses can sometimes block high-affinity antibody production. Targeted IFN-γ blockade might tip the balance toward TFH, aiding pathogen clearance or vaccine success. (7/10) 💡Mechanistic Insights: By tuning IFN-γ signals, we can reprogram local lymph nodes and “unlock” TFH potential. This points toward new avenues to combine T cell and B cell–focused therapies for more effective vaccines. (8/10) 👏Huge congratulations to Mirela Kuka, Eleonora Sala, Maria Nelli and all contributors who co-led the study! (9/10) 📖Dive deeper into our research and its implications for antiviral defense and vaccines. We look forward to your thoughts and questions! Full paper here: embopress.org/doi/full/10.10… @SanRaffaeleMI @MyUniSR @ERC_Research @AIRC_it @EMBO @ArmeniseHarvard (10/10) 💬📚