Human CD4+CD3− Innate-Like T Cells Provide a Source of TNF and Lymphotoxin-αβ and Are Elevated in Rheumatoid Arthritis

Bekiaris, Vasileios; Šedý, John; Rossetti, Maura; Spreafico, Roberto; Sharma, Shilpi; Rhode-Kurnow, Antje; Ware, Brian C.; Huang, Nini; Macauley, Matthew G.; Norris, Paula S.; Albani, Salvatore; Ware, Carl F.

doi:10.4049/jimmunol.1301672

Cited by 22 publications

(26 citation statements)

References 51 publications

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“…Further examination of ILC1 revealed that, like a recently described CD4+ CD3− innate-like T cell population (31), CD4+ ILC1 also expressed intracellular CD3ε, although we detected little or no expression of surface or intracellular TCRαβ on any peripheral blood ILC (Figure 1C, 1D). Furthermore, intracellular CD3ε was present not only in CD4+ ILC1, but in a large percentage of all ILC1 subsets, but not ILC2 or ILC3.…”

Section: Resultssupporting

confidence: 60%

CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

Roan

Stoklasek

Whalen

et al. 2016

The Journal of Immunology

103

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Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of antigen. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as ILC1 contains CD4+ CD8−, CD4− CD8+ and CD4− CD8− populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4+ ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4+ ILC1 and NKp44+ ILC3, but not CD4− ILC1 or ILC2, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology as well as immune dysregulation. Furthermore, we demonstrate that CD4+ and CD4− ILC1 are functionally divergent based on their IL-6Rα expression, and that the frequency of IL-6Rα expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4+ and CD4− ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases such as systemic sclerosis.

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Section: Resultssupporting

confidence: 60%

CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

Roan

Stoklasek

Whalen

et al. 2016

The Journal of Immunology

103

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“…We showed that other cell subsets, such as T cells, contaminated the gating strategies used typically for ILC1 identification . Consistent with these observations, various other publications have reported the expression of T cell markers on ILC1 cells, including intracellular CD3, invariant TCR (iTCR)‐β, CD5, CD8 and CD4 . As suggested, these cells could represent a heterogeneous population of innate‐like T lymphocytes or T cell‐like innate lymphocytes.…”

Section: Ilc Subset Heterogeneity In Humanssupporting

confidence: 85%

Dissecting human ILC heterogeneity: more than just three subsets

Simoni

Newell

2017

Immunology

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SummaryInnate lymphoid cells (ILCs) have been divided into three distinct groups based on functional capacities, cytokine profiles and transcription factor expression. Studies performed mainly in mice have demonstrated the importance of ILCs in chronic inflammation, infection, allergy and cancer. In this review, we discuss the heterogeneity of human ILC and focus primarily on the taxonomy of human ILC cell subsets and their phenotypical and functional diversity. We summarize recent findings concerning the diversity of ILCs between and within the major subsets [natural killer (NK), ILC1, intra-epithelial ILC1 (ieILC1), ILC2, ILC3, lymphoid tissues inducer (LTi) and ILC progenitor (ILCP)], as well as the abundance of each in human tissues. We also discuss the similarities observed between groups of cells in term of receptors expressed and cytokines produced, and how these relate to the pleiotropic properties of each subset.

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“…However, in contrast to conventional T cells, ILC1s expressed intracellular CD3ε but not surface TCRαβ or CD3ε (Roan et al 2016). In addition, a CD127 + CD4 + CD3 − innate lymphocyte population described by Bekiaris and colleagues was not activated in vitro by αCD3/αCD28 (Bekiaris et al, 2013). Although CD4 + , CD8 + and double-negative (DN) ILC1s did not express surface TCRαβ or CD3ε, most expressed CD5 (Supplemental Figure).…”

mentioning

confidence: 99%

Human Group 1 Innate Lymphocytes Are Negative for Surface CD3ε but Express CD5

Roan¹,

Ziegler

2017

Immunity

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Simoni and colleagues recently published a mass cytometry (CyTOF)-based analysis of innate lymphoid cell (ILC) subsets across different human tissues (Simoni et al., 2017). Helper-type ILC1 cells were undetectable in these analyses, and the authors suggest that ILC1s reported in previous studies were likely attributable to T cell contamination. Although much of the heterogeneity and complexity within the ILC1 population remains to be fully delineated, we believe there is ample evidence that these cells constitute a unique population(s) clearly distinct from conventional T cells.

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Human CD4+CD3− Innate-Like T Cells Provide a Source of TNF and Lymphotoxin-αβ and Are Elevated in Rheumatoid Arthritis

Cited by 22 publications

References 51 publications

CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

Dissecting human ILC heterogeneity: more than just three subsets

Human Group 1 Innate Lymphocytes Are Negative for Surface CD3ε but Express CD5

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