CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells

Björkström, Niklas K.; Béziat, Vivien; Cichocki, Frank; Liu, Lisa L.; Levine, Jeffrey; Larsson, Stella; Koup, Richard A.; Anderson, Stephen; Ljunggren, Hans Gustaf; Malmberg, Karl‐Johan

doi:10.1182/blood-2012-03-416867

Cited by 94 publications

(122 citation statements)

References 49 publications

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“…39 Additionally, although there was discordance between enrichment of multiple KIR gene transcripts in the CD8 C BTLA ¡ TIL and a few KIRs being expressed at the protein level in our present study, this might be explained by recent findings in which human CD8 C T cells, unlike NK cells, were found to generally express only one activating or inhibitory KIR. 40 Our gene expression studies also give some insights into the issue of inhibitory receptors and CD8 C T-cell exhaustion. Interestingly, we found significant enrichment of a T-cell deletion/tolerance signature in the CD8 C BTLA ¡ subset, supporting the more differentiated and hyporesponsive nature of these BTLA ¡ cells.…”

Section: Discussionmentioning

confidence: 99%

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

Haymaker

Ritthipichai

et al. 2015

OncoImmunology

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Section: Discussionmentioning

confidence: 99%

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

Haymaker

Ritthipichai

et al. 2015

OncoImmunology

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“…High CpG methylation of the KIR proximal promoter was reported in NK cells and CD8 + T cells lacking expression of the corresponding KIR molecule, and vice versa 139, 140, 141. KIR expression requires the intermediate promoter Pro1;142 however, the strength of KIR proximal promoter antisense activity is probably responsible for clonal KIR distribution in NK and T cells 7, 142, 143, 144. The relative affinity of binding sites for transcription factors involved in sense versus antisense promoter activity determines the probability of generating the sense transcript required for gene activation 142, 143.…”

Section: Kir Gene Expressionmentioning

confidence: 99%

“…Although NK cell KIR repertoire is considered stable in time, the frequency of KIR + T cells increases with age, due to accumulation of terminally differentiated T cells 141. Interestingly, HCMV‐specific CD8 T cells almost completely lack KIR expression, and the specificity of KIR‐expressing cells remains largely unknown 2, 5, 7, 151, 179. In contrast, it was shown that KIR + CD4 + T cells display specificity against HCMV but not Epstein–Barr virus or HSV‐1 4.…”

Section: Kir Gene Expressionmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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“…Concomitantly, CD8 T cells express CD45RA (TEMRA phenotype), lose CD27, CD62L, and activation markers HLA-DR and CD38, but acquire CD56 and KIR. 51 The function of terminally differentiated cells has been described as defective in many studies, but more recent data indicate that viral infections leave specific adaptive signatures on NK-and T-cell phenotype. 52,53 The absence of professional antigen-presenting cells led us to speculate that invariant T cells including invariant NK T cells, gd T cells, or MAIT cells might be relatively expanded.…”

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confidence: 99%

The evolution of cellular deficiency in GATA2 mutation

Dickinson

Milne

Jardine

et al. 2014

Blood

184

276

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• Diverse patient groups with GATA2 mutation develop mononuclear cytopenia and elevated Flt3 ligand. • Progressive cytopenias, risingFlt3 ligand, and terminal differentiation of lymphoid cells accompany clinical progression.Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56 bright NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8 1 memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making. (Blood. 2014;123(6):863-874)

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CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells

Cited by 94 publications

References 49 publications

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

The evolution of cellular deficiency in GATA2 mutation

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