Innate‐like <scp>CD</scp>8+ T‐cells and <scp>NK</scp> cells: converging functions and phenotypes

Kurioka, Ayako; Klenerman, Paul; Willberg, Christian

doi:10.1111/imm.12925

Cited by 32 publications

(43 citation statements)

References 144 publications

(283 reference statements)

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“…One possibility is that the CD8 T cells in the lesions are inducing non‐specific killing of healthy tissue. Previous studies have shown that senescent CD8 + T cells acquire the expression of functional NK receptors . Furthermore, inflammation and also the development of senescence induces the expression of NK ligands in tissue cells .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that senescent CD8 + T cells acquire the expression of functional NK receptors. 30,31 Furthermore, inflammation and also the development of senescence induces the expression of NK ligands in tissue cells. 31 Therefore, skin-homing CD8 + T cells in CL may mediate non-specific pathology by killing NKR-ligand-expressing cells such as fibroblasts and keratinocytes in the skin.…”

Section: Discussionmentioning

confidence: 99%

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Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

et al. 2020

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Summary Cytotoxic activity mediated by CD8+ T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of natural killer (NK) cell phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than age‐matched controls. The accumulation of circulating senescent NK cells (CD56dim CD57bright) correlated positively with skin lesion size in the same patients, suggesting that they, like circulating senescent CD8+ T cells, may contribute to the immunopathology of CL. However, this senescent population had lower cutaneous lymphocyte antigen expression and so had diminished skin‐homing potential compared with total or senescent CD8+ T cells. This was confirmed in CL skin lesions where we found a predominance of CD8+ T cells (both senescent and non‐senescent) that correlated with the severity of the disease. Although there was also a correlation between the proportions of senescent NK cells (CD56+ CD57+) in the skin and lesion size, this was less evident. Collectively our results demonstrate first‐hand that senescent cytotoxic cells may mediate skin pathology during human cutaneous leishmaniasis. However, as senescent cytotoxic CD8+ T cells predominate in the skin lesions, they may have a greater role than NK cells in mediating the non‐specific skin damage in CL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

et al. 2020

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“…If understanding of NK cell function is making them appear ever more adaptive in behaviour, some aspects of CD8 T-cell function are coming to be appreciated as nearer to that of innate immune populations. 9 Willberg and colleagues have pointed out the similarities between the cytokine-driven programmes of CD161 + CD8 mucosa-associated invariant T (MAIT) cells and CD56 bright NK cells. They make a persuasive case that sometimes, rather than immunology seeking to split cells into smaller and smaller subsets, it may sometimes be informative to be 'lumpers' rather than 'splitters'!…”

Section: Discussionmentioning

confidence: 99%

“…If understanding of NK cell function is making them appear ever more adaptive in behaviour, some aspects of CD8 T‐cell function are coming to be appreciated as nearer to that of innate immune populations . Willberg and colleagues have pointed out the similarities between the cytokine‐driven programmes of CD161 + CD8 mucosa‐associated invariant T (MAIT) cells and CD56 bright NK cells.…”

mentioning

confidence: 99%

Natural killer cell transcriptional control, subsets, receptors and effector function

Altmann

2019

Immunology

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Summary There have been considerable advances in characterization of the complexities of natural killer (NK) cell ligand recognition, activation, subsets and effector functions. The nature of the transcription factors that act to define distinctive functional programmes of NK cell subsets are now starting to be clarified as a consequence of studies in knockouts. Importantly, this is being extended to improved understanding of the nature of NK cell memory. As NK cell biology offers increasing resonance with analogous pathways in CD8 biology, some have made the case that immunology may sometimes benefit from a little less conceptual ‘splitting’ and a little more conceptual ‘lumping.’

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“…While altered circulating B-and NK cell frequencies may not be of direct relevance in the pathogenesis of psoriasis, 12,13,71 both lymphocyte subsets contribute to the immune response against infections, including those of a viral nature. [72][73][74] Drugs containing FAEs are used to treat psoriasis (Fumaderm â , FAEs; Skilarence â , DMF; and Psorinovo â , DMF, compounded pharmacy) and MS (Tecfidera â , DMF). All licensed FAE drugs contain DMF as the main active ingredient, which acts as an orally administered prodrug of MMF in vivo.…”

Section: Biological Effects Of Faes On Peripheral Blood Lymphocytesmentioning

confidence: 99%

Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis

Brückner

Höxtermann

Dickel³

et al. 2019

Acad Dermatol Venereol

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Background Fumaric acid esters ( FAE s) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects of FAE s on lymphocytes. Objective To evaluate the influence of long‐term FAE (Fumaderm ® ) treatment on peripheral blood CD 4 + and CD 8 + T cells, CD 19 + B cells and CD 56 + natural killer ( NK ) cells in psoriasis. Methods In this single‐centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiating FAE therapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping. Results FAE s significantly reduced the numbers of CD 4 + T, CD 8 + T, CD 19 + B and CD 56 + NK cells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest for CD 8 + T cells, with a peak of 55.7% after 2 years of therapy. The risk of T‐cell lymphopenia increased significantly with the age of the psoriasis patients at the time that FAE therapy was initiated. It was significantly decreased for the combination therapy with methotrexate and folic acid (vitamin B9) supplementation. Supporting evidence was found suggesting that T‐cell lymphopenia enhances the effectiveness of FAE therapy. Conclusions Monitoring distinct T‐cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both the FAE treatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoring CD 4 + and CD 8 + T‐cell counts at regular intervals, especially in patients of middle to older age. Thus, further prospective studies are needed to establish evidence‐based recommendations to guide dermatologists in the management of psoriasis patients who are taking FAE s and who develop low absolute T‐cell counts.

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Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

Cited by 32 publications

References 144 publications

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

Natural killer cell transcriptional control, subsets, receptors and effector function

Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis

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Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

Cited by 32 publications

References 144 publications

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8+ T cells in human cutaneous leishmaniasis

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8+ T cells in human cutaneous leishmaniasis

Natural killer cell transcriptional control, subsets, receptors and effector function

Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis

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Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis