IL-15 as a mediator of CD4 + help for CD8 + T cell longevity and avoidance of TRAIL-mediated apoptosis
- 1 April 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (13), 5201-5206
- https://doi.org/10.1073/pnas.0801003105
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.Keywords
This publication has 36 references indexed in Scilit:
- Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cellsNature, 2006
- Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell HelpScience, 2003
- Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell MemoryScience, 2003
- Reciprocal expression of TRAIL and CD95L in Th1 and Th2 cells: role of apoptosis in T helper subset differentiationCell Death & Differentiation, 2003
- Interleukin 15 Controls both Proliferation and Survival of a Subset of Memory-Phenotype CD8+ T CellsThe Journal of Experimental Medicine, 2002
- Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T CellsThe Journal of Experimental Medicine, 2002
- Effector and memory T-cell differentiation: implications for vaccine developmentNature Reviews Immunology, 2002
- T Cell MemoryAnnual Review of Immunology, 2002
- Control of Homeostasis of CD8 + Memory T Cells by Opposing CytokinesScience, 2000
- Clearance of Recombinant Vaccinia Virus Expressing IL-2: Role of Local Host Immune ResponsesCellular Immunology, 1993