CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets

Yu, Jianhua; Mao, Hsiaoyin; Min, Wei; Hughes, Tiffany; Zhang, Jianying; Park, Il-Kyoo; Liu, Shujun; McClory, Susan; Marcucci, Guido; Trotta, Rossana; Caligiuri, Michael A.

doi:10.1182/blood-2009-04-215491

Cited by 207 publications

(240 citation statements)

References 33 publications

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“…Additionally, NK cell KIR expression is related to cellular differentiation. KIR expression is weak or absent in immature NKG2A + CD56 bright NK cells and increases gradually with maturation, reaching its maximum level in NKG2A − CD56 dim NK cells 148, 149, 150. Similar observation was made for T cells, in which KIR expression is virtually absent in CD4 and CD8 naive T cells and reaches its maximal level in differentiated effector memory T cells 2, 5, 151, 152.…”

Section: Kir Gene Expressionsupporting

confidence: 68%

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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Section: Kir Gene Expressionsupporting

confidence: 68%

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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“…2,6,38,39 In the current model of NK-cell maturation, NKG2A þ cells predate KIR þ cells and CD56 bright cells predate CD56 dim cells. [24][25][26] Using this model, we did not find any difference in NK-cell maturation. 40 Our data furthermore support this model, as CD56 bright and NKG2A þ NK cells are preponderant in the first months and decrease over the first year after transplant, whereas KIR þ cells percentage increases during the same period.…”

Section: Discussionmentioning

confidence: 80%

“…[21][22][23] NK-cell maturation stages were explored by studying the CD56 bright , NKG2A þ and KIR þ cells. [24][25][26] Finally, we compared the recovery of cells involved in immune regulation, GVHD and GVL, by examining the proportion of invariant NKT (iNKT) cells within the CD3 population, [27][28][29] and CD25 þ FOXP3 þ T regulatory (Treg) cells within the CD4 þ compartment. 30,31 Together, these results reveal that NK-cell reconstitution is more sustained post-CBT than post-BMT, whereas thymopoiesis is delayed in CBT patients as compared with BM recipients.…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

Charrier

Cordeiro

Brito

et al. 2012

Bone Marrow Transplant

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Some clinical characteristics of cord blood transplantation (CBT) might be explained by specificities in the reconstitution of immune subsets differing by their maturation stage or their implication in GVHD, tolerance or immune responses against tumor or infectious agents. Here, we compare the immune reconstitution of several of these subsets after CBT and BMT. B-cell count recovery was faster after CBT. There was no difference in the recovery of CD4 þ and CD8 þ cell counts. There was no difference either in the frequency of several subsets: CD45RO þ memory, and CD45RA þ naïve cells within the CD4 þ T-cell compartment, CD27 þ among B cells, CD56 bright , NKG2A þ , and KIR þ cells among natural killer (NK) cells, CD25 þ FOXP3 þ regulatory T cells and invariant NKT cells. The proportion of the thymic naïve CD31 þ CD45RA þ CD4 þ T cells was lower after CBT at 6 months post-transplant, and was still below normal at 1 year in both groups. NK-cell expansion was more sustained after CBT, with fewer double-negative NKG2A À KIR À hyporesponsive cells and more double-positive NKG2A þ KIR þ hyper-responsive NK cells. These results, therefore, indicate that further research to improve CBT outcome should try to improve thymopoieisis and take advantage of the sustained NK-cell reconstitution. INTRODUCTIONAlmost all lethal complications of hematopoietic SCT, including leukemia relapse, and opportunistic infections, result from the post-transplant immune deficiency that lasts for months after transplantation. Therefore, the therapeutic challenge in improving the outcome for transplanted children outcome relies on the enhancement of immune reconstitution and the GVL effect, without increasing the harmful GVHD.Although lower rates of engraftment and GVHD and higher rates of life-threatening infections have been reported in patients who received cord blood transplantation (CBT), similar EFS and leukemia relapse rates have been observed after CBT and BMT. [1][2][3][4][5] These observations indicate that cord blood-derived immune cells have unique immune properties that allow for allogeneic tolerance while preserving the GVL effect.Previous studies have compared the reconstitution of the major immune cell populations after CBT and BMT: CD4 þ and CD8 þ T cells, natural killer (NK) and B cells. They showed that T-cell recovery is delayed, in particular CD8 þ T-lymphopoiesis after CBT, 2,6-9 although T-cell diversity has been shown to be similar in cord blood (CB) and BM recipients beyond 1 year after transplant. 7,10 Conversely, innate immunity recovery has been shown to be similar between CB and BM recipients, with normal cell counts of functional NK cells in the blood as soon as 1-month post-CBT. 2,11,12 Finally, B-cell number recovery appears to be faster after CBT. 6,9,13 Besides these differences in the reconstitution of the major lymphocyte populations, additional changes in the reconstitution of other immune cell subsets might occur and explain some of the clinical differences observed in patients who receive BMT or CBT.

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“…Developmentally, it now appears clear that human cytolytic CD56 dim NK cells differentiate from the less mature, noncytolytic CD56 bright NK cells (41)(42)(43)(44)(45), and the current study shows that PTEN undergoes a .5-fold reduction in protein expression during this transition. Forced overexpression of PTEN in mice did not alter NK cell differentiation as determined by the quantity of immature and mature NK cell subsets and by the acquisition of NK cell activating and inhibitory receptors; however, it did prevent the phenotypically more mature NK cell subsets from acquiring optimal cytolytic activity.…”

Section: Discussionmentioning

confidence: 88%

PTEN Is a Negative Regulator of NK Cell Cytolytic Function

Briercheck

Trotta

Chen

et al. 2015

The Journal of Immunology

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Human NK cells are characterized by their ability to initiate an immediate and direct cytolytic response to virally infected or malignantly transformed cells. Within human peripheral blood, the more mature CD56dim NK cell efficiently kills malignant targets at rest, whereas the less mature CD56bright NK cells cannot. In this study, we show that resting CD56bright NK cells express significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein when compared with CD56dim NK cells. Consistent with this, forced overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and loss of PTEN in CD56bright NK cells resulted in elevated cytolytic activity. Comparable studies in mice showed PTEN overexpression did not alter NK cell development or NK cell–activating and inhibitory receptor expression yet, as in humans, did decrease expression of downstream NK activation targets MAPK and AKT during early cytolysis of tumor target cells. Confocal microscopy revealed that PTEN overexpression disrupts the NK cell’s ability to organize immunological synapse components including decreases in actin accumulation, polarization of the microtubule organizing center, and the convergence of cytolytic granules. In summary, our data suggest that PTEN normally works to limit the NK cell’s PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic mediators toward the target cell and suggest that PTEN is among the active regulatory components prior to human NK cells transitioning from the noncytolytic CD56bright NK cell to the cytolytic CD56dim NK cells.

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CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets

Cited by 207 publications

References 33 publications

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

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

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

PTEN Is a Negative Regulator of NK Cell Cytolytic Function

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