1. Preferential Expansion of Human Virus-Specific Multifunctional Central Memory T Cells by Partial Targeting of the IL-2 Receptor Signaling Pathway: The Key Role of CD4+ T Cells
- Author
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M. Schmueck, Si-Hong Luu, Nina Babel, Petra Reinke, Henrike Fuehrer, G. Brestrich, Karin Mueller, Ben Hammoud, Annika M. Fischer, and Hans-Dieter Volk
- Subjects
CD4-Positive T-Lymphocytes ,TOR Serine-Threonine Kinases ,T cell ,ZAP70 ,Immunology ,Interleukin-2 Receptor alpha Subunit ,CD28 ,Streptamer ,Biology ,Cell biology ,Interleukin 21 ,medicine.anatomical_structure ,T-Lymphocyte Subsets ,Cytomegalovirus Infections ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Immunologic Memory ,Cells, Cultured ,Signal Transduction - Abstract
Effector memory T cells are effective in controlling acute infections, but central memory T cells play a key role in long-lasting protection against viruses and tumors. In vivo/in vitro challenge by Ag commonly supports the generation of effector memory T cells with limited longevity. To our knowledge, this study demonstrates for the first time in the human system and under rechallenge conditions that targeting IL-2R by partial mammalian target of rapamycin inhibition or blocking IL-2Rα enriches human CD4+/CD8+ central memory T cells within the virus-specific T cell product associated with enhanced functionality (i.e., multicytokine secretors, including IL-2; enhanced CD137 and CD107a expression on CD8+ and CD4+ T cells, respectively; and killing infected target cells). Remarkably, the effects on CD8+ T cells are mainly mediated via the enhancement of CD4+ T cell function. The data reveal new insights into the role of CD4+ T cell support for the quality of CD8+ T cell memory, even under rechallenge conditions. Moreover, our method offers a new approach to improve the long-lasting efficacy of adoptive T cell therapy in patients.
- Published
- 2012
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