{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:37:16Z","timestamp":1768520236024,"version":"3.49.0"},"posted":{"date-parts":[[2025,1,1]]},"group-title":"Immunology","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells play a critical role in antiviral humoral and cellular immune responses. We have previously reported that subcutaneous lymphocytic choriomeningitis virus (s.c. LCMV) infection is characterized by a stark compartmentalization of CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells, leading to strong T\n                  <jats:sub>H<\/jats:sub>\n                  1 polarization but virtually absent T follicular helper (T\n                  <jats:sub>FH<\/jats:sub>\n                  ) cells, a key driver of humoral immunity. Here, we investigated the mechanisms responsible for this impaired T\n                  <jats:sub>FH<\/jats:sub>\n                  differentiation. We found that T-bet\n                  <jats:sup>+<\/jats:sup>\n                  cells induced by s.c. LCMV infection encompass a T\n                  <jats:sub>H<\/jats:sub>\n                  1 subset expressing Granzyme-B (GzmB) and a Tcf-1\n                  <jats:sup>+<\/jats:sup>\n                  subset that retains the potential for T\n                  <jats:sub>FH<\/jats:sub>\n                  differentiation without expressing mature T\n                  <jats:sub>FH<\/jats:sub>\n                  markers. Interestingly, IFN-\u03b3 blockade enables full differentiation of Tcf-1\n                  <jats:sup>+<\/jats:sup>\n                  cells into T\n                  <jats:sub>FH<\/jats:sub>\n                  , formation of germinal centers and increased antibody production. Of note, the suppression of T\n                  <jats:sub>FH<\/jats:sub>\n                  cells by IFN-\u03b3 is not directly mediated through CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells but rather involves another cell type, likely dendritic cells (DCs). Our study provides novel insights into the mechanisms directing early CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell polarization and affecting humoral responses to viruses, laying a foundation for the development of effective vaccine strategies.\n                <\/jats:p>","DOI":"10.1101\/2024.12.31.630815","type":"posted-content","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T19:55:13Z","timestamp":1735761313000},"source":"Crossref","is-referenced-by-count":0,"title":["T cell-derived IFN-\u03b3 Suppresses T Follicular Helper Cell Differentiation and Antibody 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