IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis.

Abstract

CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-X(L) in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8+ cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.

• Authors: Sangkon Oh, Liyanage P Perera, Masaki Terabe, Ling Ni, Thomas A Waldmann, Jay A Berzofsky
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 13 Pg. 5201-6 (Apr 01 2008) ISSN: 1091-6490 [Electronic] United States
• PMID: 18362335 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Interleukin-15
• TNF-Related Apoptosis-Inducing Ligand
• Vaccines
• bcl-2-Associated X Protein
• Caspase 3

Topics

• Animals
• Antigen-Presenting Cells (immunology)
• Apoptosis (immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Caspase 3 (metabolism)
• Cell Line
• Cell Membrane (immunology, metabolism)
• Dendritic Cells (immunology, metabolism)
• Down-Regulation
• Female
• Immunologic Memory (immunology)
• Interleukin-15 (deficiency, genetics, immunology, metabolism)
• Mice
• Mice, Knockout
• Neoplasms (immunology, pathology)
• Protein Binding
• T-Lymphocytes, Helper-Inducer (immunology)
• TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Up-Regulation
• Vaccines (immunology)
• bcl-2-Associated X Protein (metabolism)