Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH)

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Abstract: Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by impaired lymphocyte cytotoxicity. First‐line therapeutic regimens directed against activated immune cells or secreted cytokines show limited efficacy since they do not target the underlying immunological problem: defective lymphocyte cytotoxicity causing prolonged immune stimulation. A potential rescue strategy would be the adoptive transfer of ex vivo gene‐corrected autologous T cells. However, transfusion of cytotoxicity‐competent T cells under conditions of hyperinflammation may cause more harm than benefit. As a proof‐of‐concept for adoptive T cell therapy (ATCT) under hyperinflammatory conditions, we transferred syngeneic, cytotoxicity‐competent T cells into mice with virally triggered active primary HLH. ATCT with functional syngeneic trigger‐specific T cells cured Jinx mice from active HLH without life‐threatening side effects and protected Perforin‐deficient mice from lethal HLH progression by reconstituting cytotoxicity. Cured mice were protected long‐term from HLH relapses. A threshold frequency of transferred T cells with functional differentiation was identified as a predictive biomarker for long‐term survival. This study is the first proof‐of‐concept for ATCT in active HLH.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH) ; day:24 ; month:10 ; year:2022 ; extent:25
EMBO molecular medicine / European Molecular Biology Organization ; (24.10.2022) (gesamt 25)

Creator: Weißert, Kristoffer
Ammann, Sandra
Kögl, Tamara
Dettmer‐Monaco, Viviane
Schell, Christoph
Cathomen, Anton
Ehl, Stephan
Aichele, Peter

DOI: 10.15252/emmm.202216085

URN: urn:nbn:de:101:1-2022102415020887969253

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:31 AM CEST

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