Interleukin 15-Mediated Induction of Cytotoxic Effector Cells Capable of Eliminating Epstein-Barr Virus-Transformed/Immortalized Lymphocytes in Culture
| Autor: | Ehsan Sharif-Askari, Ali Ahmad, Phay Tran, Lama M. Fawaz, José Menezes |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic Herpesvirus 4 Human Cancer Research Time Factors T-Lymphocytes medicine.medical_treatment Lymphocyte Biology Lymphocyte Activation Antigen medicine Humans Cytotoxic T cell Cells Cultured Cell Line Transformed Interleukin-15 B-Lymphocytes Lymphokine-activated killer cell Immunotherapy Cell Transformation Viral Virology Molecular biology Lymphocyte Subsets Recombinant Proteins Killer Cells Natural medicine.anatomical_structure Epstein-Barr Virus Nuclear Antigens Oncology Interleukin 15 Cell culture Interleukin 12 Cell Division |
| Zdroj: | JNCI Journal of the National Cancer Institute. 93:1724-1732 |
| ISSN: | 1460-2105 0027-8874 |
| Popis: | Background: Interleukin 15 (IL-15) activates cytotoxic lymphocytes and drives the expansion of memory T cells. Its role in immune control of virus-transformed cells and other tumor cells remains to be elucidated. We investigated the role of IL-15 in controlling Epstein-Barr virus (EBV)transformed/immortalized lymphocytes in culture. EBV is a highly potent lymphocyte-transforming and opportunistic oncogenic herpesvirus associated with several human tumors. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy donors were infected with EBV and cultured with either IL-15 or IL-15 plus anti-IL-15 antibodies for 3–4 weeks. We monitored EBV-induced transformation by assessing the clearly visible cell clusters by microscopy and analyzing the expression of EBV-encoded latent membrane oncoprotein-1 (LMP-1) and the EBV nuclear antigen (EBNA) complex by immunoblotting and immunofluorescence techniques, respectively. We depleted EBVinfected cultures of PBMCs of specific effector cell populations to investigate the effector cells involved in mediating IL-15 effect. Results: The presence of IL-15 resulted in the complete elimination of EBV-transformed cells in PBMC cultures. Western blot and immunofluorescence analyses performed 3–4 weeks after infection showed no detectable levels of LMP-1 and EBNA in IL-15-treated EBVinfected cultures, whereas IL-15-untreated EBV-infected cultures and IL-15/anti-IL-15-treated cultures expressed both proteins. IL-15 mediated its anti-EBV effect through early and late response mechanisms, i.e., by first activating natural killer (NK) cells and subsequently inducing cytolytic NK-T cells. The presence of anti-IL-15 neutralizing antibodies abrogated IL-15’s effect on both mechanisms. Conclusion: In vitro, IL-15 mediated complete elimination of EBVinfected/transformed lymphocytes via successive activation of NK and NK-T cytotoxic effectors. If these in vitro findings reflect in vivo mechanisms, then IL-15 might be considered for cytokine-based immunotherapy in patients with EBVassociated lymphoproliferative disorders/malignancies. [J Natl Cancer Inst 2001;93:1724–32] |
| Databáze: | OpenAIRE |
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