NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

Pallmer, Katharina; Barnstorf, Isabel; Baumann, Nicolas S.; Borsa, Mariana; Jonjić, Stipan; Oxenius, Annette

doi:10.1371/journal.ppat.1007725

Cited by 40 publications

(40 citation statements)

References 59 publications

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“…NKG2D and NKp46 have both been demonstrated to be important for the killing of virus-activated CD8 + T cells by NK cells [3,4,[7][8][9]. The role of these receptors for the regulation of CD8 + T RM cells by SG NK1.1 + cells was tested in P14 chimeric mice lacking NKG2D or NKp46.…”

Section: Increased P14 T Rm Cells By Nk11 + Cell Depletion Is Indepementioning

confidence: 99%

“…NK cells impair virus-specific T-cell responses indirectly by rapid elimination of antigen-presenting cells [1,2] or directly by cell-mediated lysis of virus-activated T cells [3][4][5][6]. Important molecules in these regulatory pathways are NKG2D and NKp46 as recogni-Correspondence: Prof. Hanspeter Pircher e-mail: pircher@ie-freiburg.mpg.de tion structures and perforin and TRAIL as effector mechanisms [4,5,[7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice

et al. 2020

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NK1.1 + cells found in salivary glands (SG) represent a unique cell population of innate lymphoid cells (ILC) with characteristics of both conventional NK cells and ILC1. Here, we demonstrate that these NK1.1 + cells limit the accumulation and differentiation of virus-specific tissue-resident memory CD8 + T cells (T RM cells) in SG of mice infected with lymphocytic choriomeningitis virus (LCMV). The negative regulation of LCMV-specific CD8 + T RM cells by NK1.1 + cells in SG is independent of NKG2D, NKp46, TRAIL, and perforin. Moreover, analysis of NKp46 iCre+ Eomes fl/fl mice revealed that Eomes-dependent conventional NK cells are dispensable for negative regulation. Since the SG are prone to autoimmune reactions, regulation of T RM cells by tissue-resident ILC may be particularly important to prevent immunopathology in this organ.

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Section: Increased P14 T Rm Cells By Nk11 + Cell Depletion Is Indepementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice

et al. 2020

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“…The absence of NCR1 increased the numbers of virus-specific CD8 T cells that leads to enhanced virus control during acute and chronic LCMV infection. However, the increased CD8 T cell responses caused a concomitant pronounced immunopathology in the setting of chronic infection [107]. Furthermore, transfer experiments of virus-specific CD8 T cells into NCR1-deficient mice revealed a direct NK-T cell cross-talk with killing of activated CD8 T cells in an NCR1-dependent manner, which shows a new pathway engaged by NK cells to modulate adaptive T-cell immunity to protect the host from severe immune-mediated damage [107].…”

Section: Nk/t Cell Interplaymentioning

confidence: 99%

The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy

Fisicaro

Rossi

Vecchi

et al. 2019

IJMS

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Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications.

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“…It is of note, however, that some viral NCR-Ls can inhibit NCR functions, representing a possible immune evasion strategy (203). It has been very recently demonstrated in mouse that NK cells may play a regulatory role during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection through the NKp46-mediated killing of LCMV-specific CD8 T cells (204).…”

Section: Role Of Nk Cells In Immune Regulationmentioning

confidence: 99%

An Historical Overview: The Discovery of How NK Cells Can Kill Enemies, Recruit Defense Troops, and More

et al. 2019

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Natural killer (NK) cells were originally defined as effector lymphocytes of innate immunity characterized by the unique ability of killing tumor and virally infected cells without any prior priming and expansion of specific clones. The “missing-self” theory, proposed by Klas Karre, the seminal discovery of the first prototypic HLA class I-specific inhibitory receptors, and, later, of the Natural Cytotoxicity Receptors (NCRs) by Alessandro Moretta, provided the bases to understand the puzzling behavior of NK cells. Actually, those discoveries proved crucial also for many of the achievements that, along the years, have contributed to the modern view of these cells. Indeed, NK cells, besides killing susceptible targets, are now known to functionally interact with different immune cells, sense pathogens using TLR, adapt their responses to the local environment, and, even, mount a sort of immunological memory. In this review, we will specifically focus on the main activating NK receptors and on their crucial role in the ever-increasing number of functions assigned to NK cells and other innate lymphoid cells (ILCs).

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NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

Cited by 40 publications

References 59 publications

NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice

NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice

The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy

An Historical Overview: The Discovery of How NK Cells Can Kill Enemies, Recruit Defense Troops, and More

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NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

Cited by 40 publications

References 59 publications

NK1.1+ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8+ T cells in mice

NK1.1+ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8+ T cells in mice

The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy

An Historical Overview: The Discovery of How NK Cells Can Kill Enemies, Recruit Defense Troops, and More

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NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice

NK1.1⁺ innate lymphoid cells in salivary glands inhibit establishment of tissue‐resident memory CD8⁺ T cells in mice