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Differential responsiveness to IL-2, IL-7, and IL-15 common receptor gamma chain cytokines by antigen-specific peripheral blood naive or memory cytotoxic CD8+ T cells from healthy donors and melanoma patients

Rosenthal, Rachel and Groeper, Célia and Bracci, Laura and Adamina, Michel and Feder-Mengus, Chantal and Zajac, Paul and Iezzi, Giandomenica and Bolli, Martin and Weber, Walter P. and Frey, Daniel M. and von Holzen, Urs and Oertli, Daniel and Heberer, Michael and Spagnoli, Giulio C.. (2009) Differential responsiveness to IL-2, IL-7, and IL-15 common receptor gamma chain cytokines by antigen-specific peripheral blood naive or memory cytotoxic CD8+ T cells from healthy donors and melanoma patients. Journal of immunotherapy, Vol. 32. pp. 252-261.

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Official URL: http://edoc.unibas.ch/dok/A6005005

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Abstract

Common receptor gamma chain (c-gamma) cytokines (CKs) support proliferation of CD8+ T cells in presence or absence of antigen triggering and help maintaining the immunologic memory. We addressed the effects of low (> or = 5 ng/mL)-dose interleukin (IL)-2, IL-7, or IL-15 on human naive and memory antigen-specific CD8+ T cells. Peripheral blood CD8+ lymphocytes proliferated with decreasing efficiency in response to IL-15, IL-7, and IL-2. Of note, IL-15 preferentially promoted expansion of CD45RA/CD8+ T-cell memory subset. Accordingly, cytotoxic T lymphocytes specific for cytomegalovirus-derived antigens from seropositive donors proliferated in response to IL-15 and, to lesser extent to IL-7, but poorly to IL-2. CD8+ T cells were then pretreated with CK before antigen stimulation using, as read out, specific cytotoxic activity. After the pretreatment with IL-15, but not IL-2, previously experienced viral antigens induced vigorous cytotoxic responses. Minor effects of IL-7 were also detectable. In contrast, IL-2 best supported the cytotoxic T lymphocyte generation from prevailingly naive CD8 T cells from HLA-A*0201 healthy donors, specific for L27Melan-A/MART-126-35 melanoma-associated antigen. Cells from melanoma patients were tested before and after Melan-A/MART-1-targeted antigen-specific immunotherapy. Untreated patients showed heterogeneous patterns of responsiveness to c-gamma CK. However, when naive patients whose CD8+ T cells best responded to IL-2 were vaccinated, a modified responsiveness pattern was detectable. After immunization, cells displayed a significantly higher response to IL-15 than to IL-2 pretreatment. Thus, responsiveness to c-gamma CK is critically influenced by naive or memory status of peripheral blood CD8+ T cells.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Klinische Forschung in der Chirurgie (Rosenthal)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Klinische Forschung in der Chirurgie (Rosenthal)
UniBasel Contributors:Adamina, Michel and Weber, Walter P. and Rosenthal, Rachel and Spagnoli, Giulio C. and Oertli, Daniel and Zajac, Paul and Bolli, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Lippincott Williams & Wilkins
ISSN:1524-9557
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:18 Dec 2015 09:32
Deposited On:24 May 2013 09:04

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