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Wnt pathway activation functionally reprograms human antigen-specific T cells
  1. Yen-Ling Chiu1,
  2. Bo-yi Sung2,
  3. Catherine Bessell3,
  4. Mathias Oelke4 and
  5. Jonathan Schneck4
  1. Aff1 grid.414746.40000000406044784Department of MedicineFar-Eastern Memorial Hospital New Taipei City Taiwan Taiwan
  2. Aff2 grid.21107.350000000121719311Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland USA
  3. Aff3 grid.21107.350000000121719311Department of Medicine, and Institute for Cell EngineeringJohns Hopkins University School of Medicine Baltimore Maryland USA
  4. Aff4 grid.21107.350000 0001 2171 9311Johns Hopkins School of Medicine, Department of PathologyInstitute for Cell Engineering Baltimore Maryland USA

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Meeting abstracts

Polyfunctionality is a hallmark of protective immunity, yet the molecular mechanisms governing polyfunctional T cells are poorly understood. After TCR activation, naïve CD8+ T cells undergo proliferation and differentiation, which lead to effector functions and memory subset development. However only a portion of activated T cells develop into memory CD8+ T cells and with chronic stimulation become terminally differentiated and exhausted CD8+ T cells, as defined by CCR7-/CD45RA+, and functionally impair effective immune responses [1]. We therefore probed the ability to reverse terminally differentiated antigen-specific cells using pharmacological agents. Stimulating human memory CD8+ T cells with cognate TCR stimulation in the presence of Wnt agonist enhances polyfunctionality and stemness. Both M1-influenza+ and CMV+ CD8+ T cell responses were reprogrammed and revealed sustained effects from initial Wnt pathway activation in vitro. Future work with cancer antigens and reprogramming of differentiated CD8+ responses could lead to improved in vitro culture conditions for adoptive immunotherapy.


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