IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells

Bérard, M; Brandt, Katja; Bulfone–Paus∥, Silvia; Tough, David F.

doi:10.4049/jimmunol.170.10.5018

Cited by 295 publications

(93 citation statements)

References 64 publications

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“…Certainly, reduced proliferation of CD8 memory T cells and a reduced CD8 memory pool are seen in mice lacking the IL-15Rα chain [131,132,133]. However, perplexingly, the proliferative effects of IL-15 on memory CD8 T cells do not require the T cells to express IL-15Rα [128,133,134,135,136]. Intriguingly, IL-15Rα instead appears to be required for cells to present IL-15 to memory T cells.…”

Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

“…Further adding to the complexity of the system, it seems that IL-15Rα must be expressed on the IL-15-producing cell for transpresentation of the cytokine to memory T cells [138, 139], possibly implying that functional IL-15 cannot be secreted in a soluble form, instead requiring externalization in complex with its receptor. The IL-2/IL-15Rβ and γc chains are required for reception of the IL-15 signal by memory T cells, and so it is believed that the low affinity of the βγ complex for IL-15 is sufficient for signal transduction [128, 133, 135, 136]. …”

Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

“…However, for CD8 memory T cells IL-15 is the more critical driver of proliferation. Supraphysiological availability of IL-15 in vivoselectively induces the proliferation and subsequent accumulation of CD8 memory T cells [105,125,126,127,128], whilst reduced proliferation and loss of CD8 memory T cells are seen in mice lacking IL-15 [40, 41, 121,129,130,131]. Based on analogy with other γc cytokines, IL-15 was presumed to signal through a trimeric receptor composed of the IL-15-specific receptor α chain (IL-15Rα) in complex with the IL-2/IL-15β and γc chains [62].…”

Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

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Homeostasis of the Memory T Cell Pool

Marsden

Kappler

Marrack

2006

Int Arch Allergy Immunol

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Memory T cells are critical for the establishment of long-term immunity. The number of memory T cells formed at the conclusion of the primary response is strongly influenced by the number of effector T cells generated in the response, but some factors can additionally enhance the efficiency and quality of memory cell recruitment. Homeostasis of the memory T cell pool depends on cytokine-mediated regulation of cell survival and proliferation. This review discusses factors that influence both the development and the maintenance of the memory T cell pool.

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Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

Section: Maintenance Of Memory Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Homeostasis of the Memory T Cell Pool

Marsden

Kappler

Marrack

2006

Int Arch Allergy Immunol

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“…IL-15 promotes basal homeostatic proliferation and survival of CD8 ϩ T M in different experimental systems (13,(15)(16)(17)(18)(19)(20)(21), whereas IL-7 performs an overlapping and complementary role during acute homeostatic proliferation in lymphopenic environments (13,18,22). In intact lymphatic compartments, IL-7 is thought to function primarily as a survival factor without providing substantial support for basal homeostatic proliferation (13,20,23).…”

mentioning

confidence: 99%

IL-7 regulates basal homeostatic proliferation of antiviral CD4 ⁺ T cell memory

Lenz

Kurz

Lemmens

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

182

195

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Heightened protection from infectious disease as conferred by vaccination or pathogen exposure relies on the effective generation and preservation of specific immunological memory. T cells are irreducibly required for the control of most viral infections, and maintenance of CD8 ؉ T cell memory is regulated by at least two cytokines, IL-7 and IL-15, which support survival (IL-7, IL-15) and basal homeostatic proliferation (IL-15) of specific CD8 ؉ memory T cells (TM). In contrast, the factors governing the homeostasis of pathogen-specific CD4 ؉ TM remain at present unknown. Here, we used a physiologic in vivo model system for viral infection to delineate homeostatic features and mechanisms of antiviral CD4 ؉ TM preservation in direct juxtaposition to CD8 ؉ T cell memory. Basal homeostatic proliferation is comparable between specific CD4 ؉ and CD8 ؉ TM and independent of immunodominant determinants and functional avidities but regulated in a tissue-specific fashion. IL-7, identified as the dominant cytokine, and IL-15, an accessory cytokine, regulate basal homeostatic proliferation and survival of antiviral CD4 ؉ TM. Interestingly, a role for these cytokines in regulation of CD4 ؉ T cell memory is not readily discernible in the generic ''memory-phenotype'' population, apparently a consequence of its heterogeneous composition. We also describe a prominent, nonredundant role for IL-7 in supporting basal homeostatic proliferation of CD8 ؉ TM. We propose that homeostatic control of antiviral CD4 ؉ and CD8 ؉ T cell memory is fundamentally similar and characterized by quantitative, rather than qualitative, differences.

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“…IFN-I plays an important role in the effector and memory fate decision process via regulating the secretion of particular cytokines (e.g., IL-15) (61)(62)(63) and the expression of the transcription factors T-bet (51) and eomesodermin (64). IFN-I receptor signaling regulates the expression of CD127 and KLRG1, which are molecules used to demarcate subsets of effector and memory T cells (49,51).…”

Section: Discussionmentioning

confidence: 99%

Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner

Qin

Shwetank

Frost

et al. 2016

J Virol

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Mouse polyomavirus (MPyV) is a ubiquitous persistent natural mouse pathogen. A glutamic acid (E)-to-glycine (G) difference IMPORTANCEIsolates of the human polyomavirus JC virus from patients with the frequently fatal demyelinating brain disease progressive multifocal leukoencephalopathy (PML) carry single amino acid substitutions in the domain of the VP1 capsid protein that binds the sialic acid moiety of glycoprotein/glycolipid receptors on host cells. These VP1 mutations may alter neural cell tropism or enable escape from neutralizing antibodies. Changes in host cell tropism can affect recruitment of virus-specific CD8 T cells. Using mouse polyomavirus, we demonstrate that a single amino acid difference in VP1 known to shift viral tropism profoundly affects the quantity and quality of the anti-polyomavirus CD8 T cell response and its differentiation into memory cells. These findings raise the possibility that CD8 T cell responses to infections by human polyomaviruses may be influenced by VP1 mutations involving domains that engage host cell receptors. Binding specificity among polyomaviruses is determined by interaction of the VP1 major capsid protein with host cell gangliosides having particular terminal sialic acid linkages (1). The gangliosides GD1a and GT1b are required for transport of mouse polyomavirus (MPyV) to the endoplasmic reticulum (2, 3). Discrete amino acid differences in the receptor binding site of VP1 impart important biological differences, including profound differences in pathogenicity (4). Replacement of the glycine (G) at position 91 of VP1 of the laboratory-derived small-plaque (SP) MPyV strain RA with glutamic acid (E), the amino acid at this position in the naturally occurring large-plaque (LP) strain PTA, was sufficient to convert it into a strain with an LP morphology and to alter the profile of induced tumors from a mesenchymal to an epithelial cell lineage (5). Alternatively, substitution of G for E at position 91 in VP1 in PTA had the opposite effect on plaque size and tumorigenicity (6, 7). In SP strains, VP1 capsids with G-91 interact with branched (␣-2,6)-linked sialyloligosaccharides, which may act as pseudoreceptors by binding cell surface glycoproteins that divert virions into noninfectious pathways (8). An E at this position in VP1 leads to electrostatic repulsion of the (␣-2,6)-linked sialic acids, thereby preventing binding of such branched structures by LP strains; however, binding to gangliosides with sialic acid (␣-2,3)-linked to galactose is retained for virion uptake into an infectious pathway (9, 10). Interestingly, MPyVs isolated from feral mice have exclusively E-91 VP1s, an unexpected finding given that such LP viruses are potentially more oncogenic than G-91 SP viruses (11).The human polyomavirus JC virus (JCV) is a frequent member of the human virome (12). Mutations of JCV capsid protein VP1

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IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells

Cited by 295 publications

References 64 publications

Homeostasis of the Memory T Cell Pool

Homeostasis of the Memory T Cell Pool

IL-7 regulates basal homeostatic proliferation of antiviral CD4 ⁺ T cell memory

Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner

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IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells

Cited by 295 publications

References 64 publications

Homeostasis of the Memory T Cell Pool

Homeostasis of the Memory T Cell Pool

IL-7 regulates basal homeostatic proliferation of antiviral CD4 + T cell memory

Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner

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IL-7 regulates basal homeostatic proliferation of antiviral CD4 ⁺ T cell memory