Your browser doesn't support javascript.
loading
Adoptively Transferred in vitro-Generated Myeloid-Derived Suppressor Cells Improve T-Cell Function and Antigen-Specific Immunity after Traumatic Lung Injury.
Kustermann, Monika; Dasari, Prasad; Knape, Ingrid; Keltsch, Emma; Liu, Jianing; Pflüger, Silvia; Osen, Wolfram; Holzmann, Karlheinz; Huber-Lang, Markus; Debatin, Klaus-Michael; Strauss, Gudrun.
Afiliação
  • Kustermann M; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Dasari P; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Knape I; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Keltsch E; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Liu J; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Pflüger S; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Osen W; GMP & T Cell Therapy, German Cancer Research Center, Heidelberg, Germany.
  • Holzmann K; Genomic-Core Facility, University Ulm, Ulm, Germany.
  • Huber-Lang M; Institute of Experimental Trauma-Immunology, University Medical Center Ulm, Ulm, Germany.
  • Debatin KM; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
  • Strauss G; Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
J Innate Immun ; : 1-18, 2022 Jun 10.
Article em En | MEDLINE | ID: mdl-35691281
Immune reactions after trauma are characterized by immediate activation of innate immunity and simultaneously downregulation of adaptive immunity leading to a misbalanced immunohomeostasis and immunosuppression of the injured host. Therefore, the susceptibility to secondary infections is strongly increased after trauma. Immune responses are regulated by a network of immune cells influencing each other and at the same time modifying their functions dependent on the inflammatory environment. Although myeloid-derived suppressor cells (MDSCs) are initially described as T-cell suppressors, their immunomodulatory capacity after trauma is mostly undefined. Therefore, in vitro-generated MDSCs were adoptively transferred into mice after blunt chest trauma (TxT). A single MDSC treatment-induced splenic T-cell expansion decreased apoptosis sensitivity and improved proliferation in the absence of T-cell exhaustion until 2 weeks after trauma. MDSC treatment had a long-lasting effect on the genomic landscape of CD4+ T cells by upregulating primarily Th2-associated genes. Remarkably, immune-activating functions of MDSCs supported the ability of TxT mice to respond to post-traumatic secondary antigen challenge. Secondary insults were mimicked by immunizing MDSC-treated TxT mice with ovalbumin (OVA), followed by OVA restimulation in vitro. MDSC treatment significantly increased the frequency of OVA-specific T cells, enhanced their Th1/Th2 cytokine expression, and induced upregulation of cytolytic molecules finally improving OVA-specific cytotoxicity. Overall, we could show that therapeutic MDSC treatment after TxT improves post-traumatic T-cell functions, which might enable the traumatic host to counterbalance trauma-induced immunoparalysis.
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Innate Immun Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Innate Immun Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha