LLT1‐mediated Activation of IFN‐γ Production in Human Natural Killer Cells Involves ERK Signalling Pathway

Bambard, Nowland D.; Mathew, Stephen O.; Mathew, Porunelloor A.

doi:10.1111/j.1365-3083.2009.02367.x

Cited by 22 publications

(23 citation statements)

References 38 publications

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“…18) and ILF3 (refs. 19, 20) are involved in the induction of ILC cytotoxic function, whereas HECT and RLD domain-containing E3 ubiquitin protein ligase 3 (HERC3) and MAP2K1 (ref. 21) are involved in enhancing the function of ILCs (i.e., classical and nonclassical MHC class I).…”

Section: Resultsmentioning

confidence: 99%

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Vaccari

Gordon

Fourati

et al. 2016

Nat Med

188

269

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A recombinant vaccine containing Aventis Pasteur’s canarypox vector (ALVAC)–HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC–simian immunodeficiency virus (SIV) and gp120 alum (ALVAC–SIV + gp120) equivalent vaccine, but not an ALVAC–SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

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Section: Resultsmentioning

confidence: 99%

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Vaccari

Gordon

Fourati

et al. 2016

Nat Med

188

269

View full text Add to dashboard Cite

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“…This secretion was reduced in the presence of anti-CD161 antibody. The effect of CD161 triggering on NK or T cell effector activities is still controversial [19], [26]. A recent report suggests that CD161 has stimulatory function on IL-17 producing CD4 T cells [27].…”

Section: Discussionmentioning

confidence: 99%

MAIT Cells Detect and Efficiently Lyse Bacterially-Infected Epithelial Cells

et al. 2013

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Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect a large variety of bacteria and yeasts. This recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (MHC) class I molecule, MR1. Here we show that MAIT cells display cytotoxic activity towards MR1 overexpressing non-hematopoietic cells cocultured with bacteria. The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells. MAIT cells are also activated by and kill epithelial cells expressing endogenous levels of MRI after infection with the invasive bacteria Shigella flexneri. In contrast, MAIT cells were not activated by epithelial cells infected by Salmonella enterica Typhimurium. Finally, MAIT cells are activated in human volunteers receiving an attenuated strain of Shigella dysenteriae-1 tested as a potential vaccine. Thus, in humans, MAIT cells are the most abundant T cell subset able to detect and kill bacteria infected cells.

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“…Similarly, while LLT1 inhibits cytotoxicity and IFN-γ production via NKR-P1A on NK cells, it appears to costimulate IFN-γ production by NKT cells (47, 107). Reciprocal studies have suggested that LLT1 itself may signal on NK and NKT cells to augment IFN-γ production via a Src-family–ERK signaling pathway (61, 152). …”

Section: Functionmentioning

confidence: 99%

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Kirkham

Carlyle

2014

Front. Immunol.

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The NKR-P1 receptors were identified as prototypical natural killer (NK) cell surface antigens and later shown to be conserved from rodents to humans on NK cells and subsets of T cells. C-type lectin-like in nature, they were originally shown to be capable of activating NK cell function and to recognize ligands on tumor cells. However, certain family members have subsequently been shown to be capable of inhibiting NK cell activity, and to recognize proteins encoded by a family of genetically linked C-type lectin-related ligands. Some of these ligands are expressed by normal, healthy cells, and modulated during transformation, infection, and cellular stress, while other ligands are upregulated during the immune response and during pathological circumstances. Here, we discuss historical and recent developments in NKR-P1 biology that demonstrate this NK receptor–ligand system to be far more complex and diverse than originally anticipated.

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LLT1‐mediated Activation of IFN‐γ Production in Human Natural Killer Cells Involves ERK Signalling Pathway

Cited by 22 publications

References 38 publications

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition

MAIT Cells Detect and Efficiently Lyse Bacterially-Infected Epithelial Cells

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

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