Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells

By Todd C. Becker, E. Wherry, D. Boone, Kaja Murali-Krishna, R. Antia, A. Ma, Rafi Ahmed. Journal of Experimental Medicine, 2002

792 citations recorded by the source corpus.

The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the generation and maintenance of virus-specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor α chain. Both cytokine- and receptor-deficient mice made potent primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV), effectively cleared the virus and generated a pool of antigen-specific memory CD8 T cells that were phenotypically and functionally similar to memory CD8 T cells present in IL-15+/+ mice. However, longitudinal analysis revealed a slow attrition of virus-specific memory CD8 T cells in the absence of IL-15 signals.This loss of CD8 T cells was due to a severe defect in the proliferative renewal of antigen-specific memory CD8 T cells in IL-15−/− mice. Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/5cc300d05abb37b8848de0f35a94d6ce2c31ed02

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In Immunology

1. Rafi Ahmed
2. E. Wherry
3. S. Kaech
4. V. Badovinac
5. J. Wherry
6. J. Harty
7. D. Masopust
8. K. Schluns

Citations in the corpus

• Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin (2005, background): “Two hallmarks of memory CD8 + T cells are their capacity for rapid recall of effector function when re-encountering a pathogen and their ability to undergo IL-15-driven proliferative renewal in the absence of pathogen attac”
• Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. (2008, background): “Long-term maintenance of these cells is antigen independent (Crotty et al., 2003; Demkowicz et al., 1996; Hammarlund et al., 2003; Lau et al., 1994; Murali-Krishna et al., 1999) and relies on interleukin 7 (IL- 7)- and IL-15-driven homeostatic proliferation ( Becker et al., 2002; Ku et al., 2000; S”
• Cytokine control of memory T-cell development and survival (2003, background): “Analysis of the kinetics of the LCMV-specific CD8 + T-cell response in IL-15-deficient mice showed that the response to three immunodominant epitopes was normal, but the response was defective to a fourth epitop”
• Heterologous immunity provides a potent barrier to transplantation tolerance. (2003, background): “ing doses of T cells (calculated number of memory cells transferred in brackets) from sensitized hosts (2 × 107 [400,000], filled squares; 107 [200,000], filled diamonds; 5 × 106 [100,000], filled triangles; 2 × 106 [40,000], open diamonds; 106 [20,000], open triangles; 2 × 107 naive cells [none], o”
• Memory CD8 T-Cell Differentiation during Viral Infection (2004, background): “The cytokines IL-7 and IL-15 are primarily responsible for this homeostatic turnover of memory CD8 T cells (14, 41, 64, 100, 101, 109).”
• Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. (2015, background): “IL-15 demonstrated activity in syngeneic murine TRAMP (Transgenic Adenocarcinoma Mouse Prostate) C2 prostatic cancer, Pmel-1 and B16 melanoma, and MC38 and CT26 colon carcinoma models.(8,21-29) On the basis of these data, an Escherichia coli (E coli) recombinant DNA– based process was developed to p”
• Shaping and reshaping CD8+ T-cell memory (2008, background): “Although the numbers of memory CD8 + T cells are stable, maintenance of memory CD8 + T-cell numbers after acute infection or vaccination is a dynamic process that involves cytokine-driven proliferation that is balanced by cell death (a process known as memory turnover”