Interleukin-15 Induces the Expression of mRNAs of Cytolytic Mediators and Augments Cytotoxic Activities in Primary Murine Lymphocytes

Ye, Weiguo; Young, John Ding‐E; Liu, Chau‐Ching

doi:10.1006/cimm.1996.0293

Cited by 62 publications

(45 citation statements)

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“…Following its initial cloning and characterization, several studies demonstrated the ability of IL-15 to induce CD8 ϩ T cell activation (14,50). However, these analyses were limited to the expression of early activation markers and secretion of cytokines by unfractionated spleen and PBMC populations (16 -19).…”

Section: Discussionmentioning

confidence: 99%

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IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

Kokaji

Hockley

Kane

2008

The Journal of Immunology

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Although the adaptive immune system has a remarkable ability to mount rapid recall responses to previously encountered pathogens, the cellular and molecular signals necessary for memory CD8+ T cell reactivation are poorly defined. IL-15 plays a critical role in memory CD8+ T cell survival; however, whether IL-15 is also involved in memory CD8+ T cell reactivation is presently unclear. Using artificial Ag-presenting surfaces prepared on cell-sized microspheres, we specifically addressed the role of IL-15 transpresentation on mouse CD8+ T cell activation in the complete absence of additional stimulatory signals. In this study we demonstrate that transpresented IL-15 is significantly more effective than soluble IL-15 in augmenting anti-CD3ε-induced proliferation and effector molecule expression by CD8+ T cells. Importantly, IL-15 transpresentation and TCR ligation by anti-CD3ε or peptide MHC complexes exhibited synergism in stimulating CD8+ T cell responses. In agreement with previous studies, we found that transpresented IL-15 preferentially stimulated memory phenotype CD8+ T cells; however, in pursuing this further, we found that central memory (TCM) and effector memory (TEM) CD8+ T cells responded differentially to transpresented IL-15. TCM CD8+ T cells undergo Ag-independent proliferation in response to transpresented IL-15 alone, whereas TEM CD8+ T cells are relatively unresponsive to transpresented IL-15. Furthermore, upon Ag-specific stimulation, TCM CD8+ T cell responses are enhanced by IL-15 transpresentation, whereas TEM CD8+ T cell responses are only slightly affected, both in vitro and in vivo. Thus, our findings distinguish the role of IL-15 transpresentation in the stimulation of distinct memory CD8+ T cell subsets, and they also have implications for ex vivo reactivation and expansion of Ag-experienced CD8+ T cells for immunotherapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

“…In vitro studies have shown that high concentrations of IL-15 can induce cellular proliferation and transcription of effector molecules such as IFN-␥ and granzyme B (grB) (14,15). Additionally, soluble IL-15 can augment anti-CD3 -induced activation and cytokine production of both mouse and human CD8 ϩ T cells (16 -19).…”

mentioning

confidence: 99%

IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

Kokaji

Hockley

Kane

2008

The Journal of Immunology

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“…Also, despite the high frequency of GzmB mRNA, the level of protein staining within long-lived memory CTLs was generally very low, indicating that the regulation of GzmB expression is more at the level of translation than of transcription. Both IL-2 and IL-15 have been demonstrated to enhance transcription of Pfp and GrzB mRNA (38,39). Given that IL-15 is important for maintenance of memory CTL homeostasis (40,41), it is tempting to speculate that the actions of IL-15 may also play a role in maintaining effector mRNA transcription in long-term influenza-specific memory CTL.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL

Jenkins

Kedzierska²,

Doherty

et al. 2007

The Journal of Immunology

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Ag-specific, CD8+ CTLs clear influenza A viruses from the lung via granzyme (Gzm) and perforin-dependent mechanisms. Ex vivo analysis of perforin-Gzm mRNA profiles demonstrated substantial heterogeneity in patterns of effector mRNA transcription of CD8+ DbNP366- or DbPA224-specific CTL. The only difference between the two epitope-specific sets was apparent very early after infection with similar molecular profiles seen in peak primary and secondary responses and in long-term memory. Surprisingly, memory T cells also expressed a diverse pattern of effector mRNA profile with an emphasis on GzmB and, surprisingly, GzmK. This analysis thus defines how naive, effector, and memory T cells differ in cytotoxic potential and provides novel insight into the molecular signatures of effector molecules observed at various stages after infection.

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“…IL-15 is particularly important because along with the γ-chain it also shares the β-chain with the IL-2 receptor. IL-15 induces the expression of perforin, GzmA, GzmB, IFN-γ, and Fas ligand in primary mouse lymphocytes (29). IL-21 works synergistically with IL-15 to upregulate GzmA and GzmB expression in mouse CD8 T cells (30).…”

Section: Extracellular Signals Regulating Granzyme Expressionmentioning

confidence: 99%

Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell Death

Chowdhury

Lieberman

2008

Annu. Rev. Immunol.

571

580

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The granzymes are cell death-inducing enzymes, stored in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, that are released during granule exocytosis when a specific virus-infected or transformed target cell is marked for elimination. Recent work suggests that this homologous family of serine esterases can activate at least three distinct pathways of cell death. This redundancy likely evolved to provide protection against pathogens and tumors with diverse strategies for evading cell death. This review discusses what is known about granzyme-mediated pathways of cell death as well as recent studies that implicate granzymes in immune regulation and extracellular proteolytic functions in inflammation.

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Interleukin-15 Induces the Expression of mRNAs of Cytolytic Mediators and Augments Cytotoxic Activities in Primary Murine Lymphocytes

Cited by 62 publications

References 0 publications

IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL

Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell Death

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