Immune reconstitution after autologous peripheral blood progenitor cell transplantation: effect of interleukin-15 on T-cell survival and effector functions

Détails

ID Serval
serval:BIB_4194B6ABE3ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Immune reconstitution after autologous peripheral blood progenitor cell transplantation: effect of interleukin-15 on T-cell survival and effector functions
Périodique
Experimental Hematology
Auteur(s)
Rutella  S., Pierelli  L., Bonanno  G., Mariotti  A., Sica  S., Sora  F., Chiusolo  P., Scambia  G., Rumi  C., Leone  G.
ISSN
0301-472X (Print)
Statut éditorial
Publié
Date de publication
12/2001
Volume
29
Numéro
12
Pages
1503-16
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
OBJECTIVE: The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic malignancies. MATERIALS AND METHODS: Patients were examined on days 30-60, 60-90, and 90-120 after PBPC infusion. Dissipation of mitochondrial transmembrane potential, a hallmark of T-cell apoptosis, has been detected using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide, after short-term T-cell culture in the absence or presence of exogenous cytokines. Expression of Bcl-2 family members has been studied by flow cytometry and reverse transcriptase polymerase chain reaction. T-cell proliferative responses to recall antigens have been estimated in autologous mixed leukocyte cultures. RESULTS: A(spont) was seen in 45% +/- 6% of CD4(+) and 55% +/- 6% of CD8(+) T cells cultured in the absence of cytokines. Of interest, IL-15 and, to a lesser extent, its structural cousin IL-2 counteracted T-cell A(spont) by inhibiting the processing of caspase-3 and up-regulating Bcl-2 mRNA and protein levels. Cell division tracking confirmed that IL-15 did not rescue T cells from A(spont) by promoting proliferation but rather acted as a genuine survival factor. Addition of a gammac-blocking antibody to cytokine-conditioned cultures abrogated both apoptosis inhibition and Bcl-2 induction by IL-15, suggesting involvement of the IL-2Rgammac signal transduction pathway. Whereas cytokine-unprimed posttransplant T cells mounted inadequate responses to recall antigens, T cells conditioned with IL-15 expanded vigorously, indicating restoration of antigen-specific proliferation. CONCLUSIONS: T cells recovering after autologous PBPC transplantation are highly susceptible to spontaneous apoptosis in vitro. This phenomenon can be counteracted by the gammac-signaling cytokine IL-15. These findings suggest that IL-15 might be a promising immunomodulating agent to improve postgrafting T-cell function.
Mots-clé
Actins/genetics Adult Antigens, CD/analysis Apoptosis/drug effects/immunology Cell Survival/*physiology Cytokines/pharmacology Female Hematologic Neoplasms/immunology/*therapy Hematopoietic Stem Cell Transplantation Humans Immunophenotyping Interleukin-15/*pharmacology Interleukin-2/pharmacology Male Middle Aged Proto-Oncogene Proteins/genetics *Proto-Oncogene Proteins c-bcl-2 Reverse Transcriptase Polymerase Chain Reaction Signal Transduction T-Lymphocytes/*immunology/pathology Transplantation, Autologous/immunology bcl-2-Associated X Protein
Pubmed
Web of science
Création de la notice
28/01/2008 9:33
Dernière modification de la notice
03/03/2018 16:34
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