{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:02:55Z","timestamp":1780470175396,"version":"3.54.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      CD100\/SEMA4D functions as a critical co-stimulatory molecule in T cell responses, existing in both membrane-bound (mCD100) and soluble (sCD100) forms. Previous studies have shown that CD100 enhances CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses indirectly by promoting the maturation and activation of antigen-presenting cells, thereby facilitating viral clearance. However, whether mCD100, highly expressed on resting T cells, can also directly regulate CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell function upon ligand engagement remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined the impact of CD100 deficiency on the functional phenotype and differentiation of HBcAg-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells using separate and co-culture systems\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Furthermore, through adoptive transfer of CD100 knockout HBV Cor93 TCR-transgenic (CD100KO C93-TCRtg) CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, we investigated the early impact of mCD100 deficiency on the development of HBcAg-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses during HBV infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The absence of mCD100 expression significantly decrease HBcAg-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell proliferation, activation, effector cytokine production, and expression of Granzyme B and Eomes upon antigen stimulation\n                      <jats:italic>in vitro<\/jats:italic>\n                      . In the acute self-resolving models, the early proliferation of transferred CD100KO C93-TCRtg CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were impaired compared to their WT counterparts following HBV challenge. Transcriptomic data revealed that significant downregulation of gene sets associated with the PI3K-Akt, mTOR, NF-\u03baB, and JAK-STAT signaling pathways in CD100KO CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Membrane CD100 expressed on resting HBcAg-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells may function as a co-stimulatory molecule by providing a direct stimulatory signal for the early proliferation and effector differentiation of T cells. The observed effects of mCD100 are associated with the PI3K-Akt-mTOR, JAK-STAT and NF-\u03baB signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1826036","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:07:52Z","timestamp":1780466872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell-autonomous co-stimulatory function of membrane-bound CD100 promotes activation and differentiation of HBcAg-specific CD8+ T cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengxiao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuecheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Sutter","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital Essen, University of Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengji","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital Essen, University of Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieliang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and 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