The Phenotypic Heterogeneity of Human Natural Killer Cells: Presence of at least 48 Different Subsets in the Peripheral Blood

Jonges, Liesbeth E.; Albertsson, Per; Vlierberghe, Ronald L.P. van; Ensink, N. G.; Br, Johansson; Velde, Cornelis J.H. van de; Fleuren, Gert Jan; Nannmark, Ulf; Kuppen, Peter J. K.

doi:10.1046/j.1365-3083.2001.00838.x

Cited by 65 publications

(45 citation statements)

References 34 publications

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“…Our results demonstrate that immune effector cells localise to sites of tumour in responding patients and that both CD4 and CD8 T-cell subsets are requisite for the response to IL-2 based immunotherapy. This is in accordance with findings in metastatic malignant melanoma treated with IL-2 (Rubin et al, 1989) and IFN-a (Hakansson et al, 1996;2001). Thus, there seems to be a causative relationship between intratumoral lymphocyte subsets and both response and survival, as indicated by the fact that progressing patients had very few intratumoral lymphocyte subsets at both baseline and during treatment.…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

et al. 2002

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The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes ( P =0.028), CD3 ( P =0.017), CD57 ( P =0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 ( P =0.027), CD8 ( P =0.028), CD57 ( P =0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 ( P =0.026), CD8 ( P =0.015), CD57 ( P =0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 ( P =0.047), baseline CD57 ( P =0.035), CD3 at one month ( P =0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients. British Journal of Cancer (2002) 87 , 194–201. doi: 10.1038/sj.bjc.6600437 www.bjcancer.com © 2002 Cancer Research UK

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Section: Discussionsupporting

confidence: 89%

“…However, NK cells show phenotypic heterogeneity in the peripheral blood (Jonges et al, 2001). Thus, the CD56 molecule is present on almost all NK cells, whereas the CD57 molecule is only present on a subpopulation of the total NK cells (Brittenden et al, 1996;Jonges et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

et al. 2002

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“…Nevertheless, information on the immunophenotypic changes occurring after NK-cell activa-tion "in vivo" is scanty and the few studies that have been published to date on this subject are restricted to the evaluation of a limited number of activation-related markers (30 -32). The fact that blood NK-cells are heterogeneous (33) and that the typical immunophenotypic patterns observed in normal non-stimulated and stimulated NK-cells are far from being well-characterized, makes it difficult to distinguish between resting/activated normal polyclonal NK-cells and their neoplastic counterparts. Moreover, in the diagnosis of NK-cell leukemia/lymphoma molecular studies are not as useful as for T-and B-cell disorders-NK-cells do not rearrange the TCR genes and other alternatives such as Xlinked molecular analysis frequently are either not applicable or not available (34,35)-imposing additional difficulties in distinguishing normal from neoplastic NK-cells.…”

Section: Introductionmentioning

confidence: 99%

The “ex Vivo” Patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR Expression Identify Acute/Early and Chronic/Late NK-Cell Activation States

Lima

Almeida

Teixeira

et al. 2002

Blood Cells, Molecules, and Diseases

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ABSTRACT:To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56 ϩ NK-cells, present in normal blood samples, usually were CD2 Ϫ/ϩlo , CD7 ϩhi , HLA-DR Ϫ , CD11b ϩ , CD38 ϩ , CD11a ϩhi , CD45RA ϩhi , and CD45RO Ϫ , the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c ϩ and CD57 Ϫ/ϩlo . Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2 ϩhi /CD7 Ϫ/ϩlo immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57 ϩ and CD11c Ϫ/ϩ . At this stage, most NK-cells had already reverted into their original CD45RA ϩ /CD45RO Ϫ /HLA-DR Ϫ phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in "in vivo" models. © 2002 Elsevier Science (USA)

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“…This is largely due to the fact that, whereas NK and T cells are well established to evolve from common pluripotential cells [1][2][3][4], a question remains unanswered as to at which stage the NK phenotypes emerges. A family of NK cells is definitely innate lymphocyte effector cells, but is distinct from a classic family of T cells in that functional cytolysistriggering receptors such as NKp46, NKp44 and NKp30 are apparently expressed [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…A family of NK cells is definitely innate lymphocyte effector cells, but is distinct from a classic family of T cells in that functional cytolysistriggering receptors such as NKp46, NKp44 and NKp30 are apparently expressed [5][6][7]. Despite such puzzling phenotypes, a general consensus is that NK cells are composed of a large family of lymphocytes, which includes NK-T, NK-CTL, CD8αα+ NK, CD3+ NK, decidual and intestinal NK cells [1,3,4,[8][9][10]. Because of their ability to purge transformed cells in vitro, the viable NK cells and their genetically engineered variants [for example, ref [11][12][13] may have potential values in clinical applications such as biological therapies.…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis of CD8+ NK/T cell line, ‘SRIK-NKL’, with array-based CGH (aCGH), SKY/FISH and molecular mapping

et al. 2008

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We performed aCGH, SKY /FISH, molecular mapping and expression analyses on a permanent CD8+ NK/T cell line, 'SRIK-NKL' established from a lymphoma (ALL) patient, in attempt to define the fundamental genetic profile of its unique NK phenotypes. aCGH revealed hemizygous deletion of 6p containing genes responsible for hematopoietic functions. The SKY demonstrated that a constitutive reciprocal translocation, rcpt(5;14)(p13.2;q11) is a stable marker. Using somatic hybrids containing der(5) derived from SRIK-NKL, we found that the breakpoint in one homologue of no. 5 is located upstream of IL7R and also that the breakpoint in no. 14 is located within TRA@. The FISH analysis using BAC which contains TRA@ and its flanking region further revealed a ~231 kb deletion within 14q11 in the der(5) but not in the normal homologue of no. 14. The RT-PCR analysis detected mRNA for TRA@ transcripts which were extending across, but not including, the deleted region. IL7R was detected at least at mRNA levels. These findings were consistent with the immunological findings that TRA@ and IL7R are both expressed at mRNA levels and TRA@ at cytoplasmic protein levels in SRIK-NKL cells. In addition to rept(5;14), aCGH identified novel copy number abnormalities suggesting that the unique phenotype of the SRIK-NKL cell line is not solely due to the TRA@ rearrangement. These findings provide supportive evidence for the notion that SRIK-NKL cells may be useful for studying not only the function of NK cells but also genetic deregulations associated with leukemiogenesis.

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The Phenotypic Heterogeneity of Human Natural Killer Cells: Presence of at least 48 Different Subsets in the Peripheral Blood

Cited by 65 publications

References 34 publications

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The “ex Vivo” Patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR Expression Identify Acute/Early and Chronic/Late NK-Cell Activation States

Genomic analysis of CD8+ NK/T cell line, ‘SRIK-NKL’, with array-based CGH (aCGH), SKY/FISH and molecular mapping

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