Expression Patterns of Killer Cell Immunoglobulin-Like Receptors (KIR) of NK-Cell and T-Cell Subsets in Old World Monkeys

Abstract Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.

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Multinomial modelling of TB/HIV co-infection yields a robust predictive signature and generates hypotheses about the HIV+TB+ disease state

10.1101/497842 ◽

2018 ◽

Author(s):

Fergal J Duffy ◽

Ethan G. Thompson ◽

Thomas J. Scriba ◽

Daniel E Zak

Keyword(s):

Machine Learning ◽

T Cell ◽

Nk Cell ◽

Expression Patterns ◽

Predictive Performance ◽

Cell Receptor ◽

Disease State ◽

Disease States ◽

Signature Genes ◽

Distinct Disease

AbstractBackgroundCurrent diagnostics are inadequate to meet the challenges presented by coinfection with Mycobacterium tuberculosis (Mtb) and HIV, the leading cause of death for HIV-infected individuals. Improved characterisation of Mtb/HIV coinfection as a distinct disease state may lead to better identification and treatment of affected individuals.MethodsFour previously published TB and HIV co-infection related datasets were used to train and validate multinomial machine learning classifiers that simultaneously predict TB and HIV status. Classifier predictive performance was measured using leave-one-out cross validation on the training set and blind predictive performance on multiple test sets using area under the ROC curve (AUC) as the performance metric. Linear modelling of signature gene expression was applied to systematically classify genes as TB-only, HIV-only or combined TB/HIV.ResultsThe optimal signature discovered was a single 10-gene random forest multinomial signature that robustly discriminates active tuberculosis (TB) from other non-TB disease states with improved performance compared with previously published signatures (AUC: 0. 87), and specifically discriminates active TB/HIV co-infection from all other conditions (AUC: 0.88). Signature genes exhibited a variety of transcriptional patterns including both TB-only and HIV-only response genes and genes with expression patterns driven by interactions between HIV and TB infection states, including the CD8+ T-cell receptor LAG3 and the apoptosis-related gene CERKL.ConclusionsBy explicitly including distinct disease states within the machine learning analysis framework, we developed a compact and highly diagnostic signature that simultaneously discriminates multiple disease states associated with Mtb/HIV co-infection. Examination of the expression patterns of signature genes suggests mechanisms underlying the unique inflammatory conditions associated with active TB in the presence of HIV. In particular, we observed that disregulation of CD8+ effector T-cell and NK-cell associated genes may be an important feature of Mtb/HIV co-infection.

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Peripheral Blood Immunological Features Associated with Aortic Valve Disease and Ascending Throcic Aorta Aneurysm and Dilation

Journal of Universal College of Medical Sciences ◽

10.3126/jucms.v3i1.13252 ◽

2015 ◽

Vol 3 (1) ◽

pp. 11-20

Author(s):

Kaushal Kishore Tiwari ◽

Silverio Sbrana ◽

Stefano Bevilacqua ◽

Paola Giungato ◽

Angela Pucci ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Aortic Valve ◽

Peripheral Blood ◽

Chemokine Receptors ◽

Aortic Valve Disease ◽

Nk Cell ◽

Valve Disease ◽

T Cell Subsets ◽

Group A

INTRODUCTION: Ascending thoracic aortic aneurysm (TAA) is a multi-factorial process in which histological modifications and immune-mediated inflammation are closely associated. The predominant role of a Th1-mediated response in influencing aortic wall remodeling, dilation, and aneurysm formation has been suggested by previous studies. Recently, the importance of chemokine receptors for Th1 cells recruitment into vascular inflammatory sites, as well as of the balance between pro- and anti-inflammatory T-cell subsets in influencing the severity of coronary artery disease, have been described.MATERIAL AND METHODS: We evaluated activation markers and chemokine receptors expression on peripheral T-cell and NK cell subsets of subject with aortic valve disease associated with ascending TAA (ascending aortic diameter > 4 cm) and undergoing elective surgery for TAA (Group A), in comparison with patients with aortic valve disease without TAA (ascending aortic diameter < 4 cm) (Group B). Peripheral blood samples from the two groups were also compared for intracellular T-lymphocyte cytokine production, frequency of regulatory T cells (Treg) and soluble levels of cytokine and chemokines. The aortic size index (ASI) was considered a parameter able to reflect aortic pathophysiological modifications leading to aortic dilation.RESULTS: The results demonstrated correlations between ASI values and CCR5 expression on CD3+, CD3+/CD8+, CD4+ and CD4+/CD28- T-cell subsets. In Group A the expression of CCR5 was higher on CD3+/CD8+, CD4+ and CD4+/CD28- T-cell subsets, when compared with Group B. CD4+ and CD4+/CD28- T-cells in Group A showed also a higher expression for the co-stimulatory molecule CD28 and the activation marker CD25, respectively. An increased expression of CXCR3 was found on CD4+, CD3+/CD8+ and CD3+/TCR+ T-cell subsets in Group A. A higher circulating fraction of NK cells, together with a higher NK cell positivity for CX3CR1, were observed in aneurysmatic patients. Intracellular cytokine analysis demonstrated a higher fraction of CD3+/CD4+ T-cells producing IL-17A and IL-10 in Group A, together with a higher intracellular content for IL-21. Finally, a higher soluble level of fractalkine (CX3CL1) has been detected in aneurysm group.CONCLUSION: Results indicate a higher activation state, migratory capacity and cytotoxic potential of peripheral blood NK and T-cell subsets in patients with aortic valve disease associated with ascending TAA, when compared with patients affected by aortic valve disease alone. These findings, together with the observed higher polarization towards a Th17 in patients with aortic aneurysm could suggest the involvement of autoimmune mechanisms leading to cellular loss, inflammation and fibrosis during ascending aortic wall dilation and aneurysmatic progression.Journal of Universal College of Medical Sciences Vol. 3, No. 1, 2015: 11-20

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Observed Changes in Natural Killer and T cell Phenotypes with Evaluation of Immune Outcome in a Longitudinal Cohort Following Sofosbuvir-Based Therapy for Chronic Hepatitis C Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz223 ◽

2019 ◽

Vol 6 (6) ◽

Cited By ~ 3

Author(s):

Timothy J Stevenson ◽

Youssef Barbour ◽

Brian J McMahon ◽

Lisa Townshend-Bulson ◽

Annette M Hewitt ◽

...

Keyword(s):

T Cells ◽

Chronic Hepatitis ◽

Hepatitis C ◽

T Cell ◽

Natural Killer ◽

Chronic Hepatitis C ◽

Nk Cell ◽

Cell Subset ◽

T Cell Subsets ◽

Immune Marker

Abstract Background Chronic hepatitis C virus (HCV) infection diminishes immune function through cell exhaustion and repertoire alteration. Direct acting antiviral (DAA)-based therapy can restore immune cell subset function and reduce exhaustion states. However, the extent of immune modulation following DAA-based therapy and the role that clinical and demographic factors play remain unknown. Methods We examined natural killer (NK) cell, CD4+, and CD8+ T cell subsets along with activation and exhaustion phenotypes across an observational study of sofosbuvir-based treatment for chronic HCV infection. Additionally, we examined the ability of clinical variables and duration of infection to predict 12 weeks of sustained virologic response (SVR12) immune marker outcomes. Results We show that sofosbuvir-based therapy restores NK cell subset distributions and reduces chronic activation by SVR12. Likewise, T cell subsets, including HCV-specific CD8+ T cells, show reductions in chronic exhaustion markers by SVR12. Immunosuppressive CD4+ regulatory T cells decrease at 4-weeks treatment and SVR12. We observe the magnitude and direction of change in immune marker values from pretreatment to SVR12 varies greatly among participants. Although we observed associations between the estimated date of infection, HCV diagnosis date, and extent of immune marker outcome at SVR12, our regression analyses did not indicate any factors as strong SVR12 outcome predictors. Conclusion Our study lends further evidence of immune changes following sofosbuvir-based therapy. Further investigation beyond SVR12 and into factors that may predict posttreatment outcome is warranted.

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Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education

Blood ◽

10.1182/blood-2010-04-281675 ◽

2010 ◽

Vol 116 (19) ◽

pp. 3853-3864 ◽

Cited By ~ 414

Author(s):

Niklas K. Björkström ◽

Peggy Riese ◽

Frank Heuts ◽

Sandra Andersson ◽

Cyril Fauriat ◽

...

Keyword(s):

Immune System ◽

Cell Differentiation ◽

Nk Cells ◽

Nk Cell ◽

Expression Patterns ◽

Killer Cell ◽

Human Leukocyte ◽

Phenotypic Properties ◽

Hematopoietic Stem ◽

Nk Cell Differentiation

Abstract Natural killer (NK) cells are lymphocytes of the innate immune system that, following differentiation from CD56bright to CD56dim cells, have been thought to retain fixed functional and phenotypic properties throughout their lifespan. In contrast to this notion, we here show that CD56dim NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57, change their expression patterns of homing molecules, and display a gradual decline in proliferative capacity. All cellular intermediates of this process are represented in varying proportions at steady state and appear, over time, during the reconstitution of the immune system, as demonstrated in humanized mice and in patients undergoing hematopoietic stem cell transplantation. CD56dim NK-cell differentiation, and the associated functional imprint, occurs independently of NK-cell education by interactions with self–human leukocyte antigen class I ligands and is an essential part of the formation of human NK-cell repertoires.

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Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers12082171 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2171

Author(s):

Isabel Valhondo ◽

Fakhri Hassouneh ◽

Nelson Lopez-Sejas ◽

Alejandra Pera ◽

Beatriz Sanchez-Correa ◽

...

Keyword(s):

T Cells ◽

Acute Myeloid Leukemia ◽

T Cell ◽

Healthy Volunteers ◽

Nk Cells ◽

Myeloid Leukemia ◽

Cell Activation ◽

Nk Cell ◽

T Cell Subsets ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

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Natural Killer Cell Immune Reconstitution Predicts Outcomes for Patients with Chronic Lymphocytic Leukemia Undergoing Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v112.11.3300.3300 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3300-3300

Author(s):

Don Benson ◽

Leslie Andritsos ◽

Mehdi Hamadani ◽

Thomas Lin ◽

Joseph Flynn ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Nk Cells ◽

Cd8 T Cells ◽

Immune Reconstitution ◽

Nk Cell ◽

Disease Status ◽

Lymphocytic Leukemia ◽

T Cell Subsets ◽

Cell Recovery

Abstract Introduction: Chronic lymphocytic leukemia (CLL), the most common form of leukemia in the Western hemisphere, is associated with severe innate, adaptive and humoral immune dysregulation. CLL remains essentially incurable, with the potential exception of allogeneic stem cell transplantation (ASCT). Natural killer (NK) cells are CD56(+), CD3(−) large granular lymphocytes that comprise a key cellular subset of the innate immune system. Preliminary in vitro data suggest an NK cell versus CLL effect exists, similar to that observed in acute myeloid leukemia (AML) and other blood cancers. Novel immune therapies for CLL (e.g., rituximab, alemtuzumab) likely exert anti-tumor effect, in part, through NK cells, in fact. Although NK cells contribute to the graft-versus-tumor effect following ASCT for other blood cancers, little is known regarding the potential role NK cells may play in the clinical allogeneic transplant setting for CLL. Herein, we provide, to our knowledge, the first report regarding NK cell immune reconstitution following ASCT for CLL. Methods: 27 CLL patients underwent reduced intensity conditioning (RIC) with ASCT. Median age was 52 years (43–69), median number of prior therapies was 3 (2–11). 55% had chemotherapy-refractory disease, and 55% had “high-risk” cytogenetics by FISH (deletion 17p or 11q22-23 abnormality). 14 patients had sibling donors, 15 had volunteerunrelated donors. Conditioning regimens included Fludarabine/TBI/Alemtuzumab (n=8), Fludarabine/Busulfan with (n=9) or without ATG (n=6), and Fludarabine/Cyclophosphamide (n=4). GVHD prophylaxis consisted of tacrolimus/MMF (n=8) or tacrolimus/methotrexate (n=19). Patients underwent bone marrow assessment prior to day +75 following ASCT. Marrow was studied for engraftment, donor chimerism, and disease status as well as lymphoid immune reconstitution by percentage of total lymphocytes and absolute lymphocyte counts by multi-color flow cytometry. Results: NK cell immune reconstitution was predicted by disease status at transplantation. Patients in complete or partial remission at the time of ASCT had more robust NK cell recovery (mean = 45% of total lymphocytes +/− SEM 5%) as compared to patients entering transplant with refractory disease (16% +/− 1, p < 0.01). No differences were observed in CD4(+) or CD8(+) T cells and no lymphocyte subset recovery was associated with CD34(+) or CD3(+) cell dosage. Achieving complete donor chimerism by day +60 was associated with robust NK cell recovery (55% +/− 1 versus 7% +/−1, p = 0.02), recovery of CD4 and CD8 T cells was not associated with chimerism status, however. Patients who went onto exhibit a complete response to ASCT had greater early NK cell reconstitution (31% +/− 3) as compared to those who had no response (8% +/− 1, p = 0.01). No differences in T cell subsets were associated with response. Patients who ultimately achieved complete remission following transplant had a lower CLL:NK cell ratio in marrow (0.35 +/− 0.07) than those who did not (8.1 +/− 1, p = 0.01). However, differences in CLL:CD4(+) and CLL:CD8(+) T cells were not predictive of response. Trends to improvement in progression free survival and overall survival were observed for patients with NK cell reconstitution above the median for the group as compared to those below; no such trends were observed regarding T cell subsets. Greater NK cell reconstitution trended towards ultimate eradication of minimal residual disease following ASCT, but no such trends were observed for T cell subsets. Conclusions: Early NK cell recovery predicts survival following autologous and allogeneic SCT in a number of hematologic malignancies; however, little is known regarding this phenomenon in CLL. To our knowledge, these are the first findings to implicate a potentially important therapeutic role for early NK cell compartment recovery in CLL following ASCT. Further research into restoring and augmenting NK cell function following RIC/ASCT for CLL is warranted.

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Changes of Immunoregulatory Cells Associated with Psychological Stress and Humor

Perceptual and Motor Skills ◽

10.2466/pms.1997.84.3c.1296 ◽

1997 ◽

Vol 84 (3_suppl) ◽

pp. 1296-1298 ◽

Cited By ~ 9

Author(s):

Tsutomu Kamei ◽

Hiroaki Kumano ◽

Sumio Masumura

Keyword(s):

T Cell ◽

Natural Killer Cell ◽

Natural Killer ◽

Psychological Stress ◽

Natural Killer Cell Activity ◽

Killer Cell ◽

Cell Activity ◽

T Cell Subsets ◽

Killer Cell Activity ◽

Before And After

For 8 medical students influences of psychological stress or humor on T-cell subset percentages and natural killer cell activity were investigated by measuring these parameters before and after an examination and before and after watching a comedy video. Although T-cell subsets were not significantly affected by either stimulus and natural killer cell activity was not affected by the examination, the latter was significantly decreased after watching the comedy video.

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Effects of Environmental Temperature on the Population of T-cell Subsets, the Blastogenic Responses of Lymphocytes in Blood and Spleen and Splenic NK cell Activity in Mice

EXPERIMENTAL ANIMALS ◽

10.1538/expanim1978.39.3_389 ◽

1990 ◽

Vol 39 (3) ◽

pp. 389-396 ◽

Cited By ~ 4

Author(s):

Tomoyuki UEDA

Keyword(s):

T Cell ◽

Environmental Temperature ◽

Nk Cell ◽

Cell Activity ◽

T Cell Subsets ◽

Nk Cell Activity

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