Changes In Natural Killer Cells Research Articles

P032 Distinct immune cell trigger responses in Ulcerative Colitis – Results from an in vivo human intestinal injury model

Abstract Background Ulcerative colitis (UC) is characterized by alternated periods of active inflammation and quiescent disease. The mechanisms behind flare-up reactions are elusive, but it is hypothesized that normally unharmful factors can initiate flares in genetically susceptible individuals with a dysfunctional mucosal barrier and hyper-responsive immune system, leading to sustained inflammation. We aimed to describe the early cellular responses to injury in the normal intestine and in UC patients in remission. Methods Experimental injuries were performed in six UC patients in remission (endoscopic Mayo sub-score 0 and total Mayo score below 3) and in six control subjects1. During the initial sigmoidoscopy, six experimental wounds were made. After 24 and 48 hours, the subjects were re-endoscoped and new biopsies were taken across the experimental injury by angling the biopsy forceps 90° (Figure 1), thus including the mucosa of the injury edge and the wound bed. Biopsies from each time point were sequenced (bulk RNA-sequencing) and the frequencies of different cell types were inferred using deconvolution (Cellanneal)2 Results Type 1-conventional dendritic cells (cDC) and macrophages decreased in both UC and controls after injury (p<0.05). Inflammatory monocytes increased in controls only at 48h post-injury, while in UC, these cells increased at 24h and decreased at 48h post-injury. There were no significant changes in natural killer cells or T and B cells frequencies between UC and controls both pre- and post-injury. The frequency of ILCs, mast cells, and type 2-cDC continuously increased in UC patients from pre-injury to 48h post-injury, in contrast to controls, where they decreased (Figure 2). ILC marker CD117 (expressed by ILC3 and ILC2) was overexpressed in UC pre-injury, however both CRTH2 (expressed only by ILC2) and CD127 were similar pre- and post-injury. Finally, the cytokines required for ILC3 stimulation (interleukin (IL)-1β, IL-1α and IL-23) and IL-17A, produced by ILC3 during inflammation, were increased. Conclusion UC patients in complete remission show an increased innate inflammatory response to mucosal injuries compared to healthy individuals, highlighted by the early engagement of inflammatory monocytes, mast cells, and ILCs, particularly ILC3s. Our data show a UC-specific innate cellular hyper-response that may explain the initial mechanisms of flares and could be targeted in future anti-flare therapies.

Changes of natural killer cells' phenotype in patients with chronic hepatitis B in intermittent interferon therapy.

To investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators. The CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry. In the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011). During the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.

S928 Effect of Etrasimod on Circulating Lymphocytes in Patients With Moderately to Severely Active Ulcerative Colitis: Data From the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 Trials

Introduction: Etrasimod (ETR), is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). Previous reports in healthy volunteers demonstrated selective effects of ETR on adaptive immune cell subsets with little effect on innate cells; however, the impact is unknown in patients with UC. Here, we report the effect of ETR on circulating immune cells in adults with moderately to severely active UC from the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. Methods: In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), adults (16-80 years) with moderately to severely active UC and documented history of inadequate response, loss of response, or intolerance to ≥1 treatment for UC were randomized 2:1 to once-daily treatment with ETR 2 mg or placebo (PBO). In this exploratory analysis, whole blood was collected throughout the studies for characterization of immune cell subsets by flow cytometry. Mean (SE) percent change from baseline (in cells/μL) to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 in ELEVATE UC 52 and Weeks 2, 4, 8, and 12 in ELEVATE UC 12 were compared between ETR 2 mg and PBO using 2-sided t tests. Results: Whole blood from 433 patients in ELEVATE UC 52 (ETR 2 mg, n=289; PBO, n=144) and 349 patients in ELEVATE UC 12 (ETR 2 mg, n=236; PBO, n=113) was included for immunophenotyping. Treatment with ETR 2 mg resulted in rapid mean (SE) percent reductions (in cells/μL) from baseline to Week 2, with nadir or near nadir changes from baseline reached by Week 4 in ELEVATE UC 52 and ELEVATE UC 12, respectively, for total T cells (CD3+: −55.6% [1.50] and −55.9% [1.65]), T helper cells (CD3+CD4+: −71.1% [1.33] and −72.5% [1.30]), cytotoxic T cells (CD3+CD8+: −35.7% [1.94] and −33.8% [2.60]), and B cells (CD3−CD19+: −74.5% [1.05] and −75.2% [1.18]); reductions were maintained through Week 52 in ELEVATE UC 52 and Week 12 in ELEVATE UC 12. There were no notable changes in natural killer cells (CD3−CD56+CD16+) or monocytes (CD14+) during the treatment period of either study. Conclusion: Treatment with ETR has a rapid and differential effect on the frequency of circulating immune cell subsets in peripheral blood in patients with moderately to severely active UC. These findings may help explain the 5 serious infections in PBO and 3 in ETR observed in the ELEVATE UC 52 and ELEVATE UC 12 trials and the balanced overall infection rates across treatment arms in both studies.

Acoustofluidic Stimulation of Functional Immune Cells in a Microreactor (Adv. Sci. 16/2022)

Acoustofluidic Stimulation of Functional Immune Cells In article number 2105809, Jinsoo Park, Hyung Jin Sung, Jessie S. Jeon, and co-workers employ surface acoustic waves to agitate fluid in a microreactor capable of dynamic cell culture in a controllable and contact-free manner. This microreactor prevents cellular damages that can be seen in the acoustic vortex by adjusting the duty cycle and applied power of the acoustical actuation. Using the microreactor, the functional changes of natural killer cells are observed upon the acoustical stimulation, namely, Ca2+ influx to the cells and their enhanced cell-mediated cytotoxicity to the tumor cells in the copresence of protein kinase C activator.

Research progress on the role of immune cells in Brucella infection

Abstract Brucellosis is one of the most prevalent zoonoses in the world. Incidence of the disease has increased significantly in recent years and has seriously affected the health of human beings and the development of animal husbandry. The pathogenesis of brucellosis remains unclear. Current studies suggest that this disease may be related to changes in natural killer cells, dendritic cells, and macrophages in immune cell subsets. Brucellosis may be also related to T helper (Th) 1 cell/Th2 cell imbalance in the CD4+ T cell subset, immunoregulation of regulatory T cells and Th17 cells, and the mechanism of action of CD8+ T cell. This paper aims to review the research progress on these inherent immune cells, the CD4+ T cell subset, and CD8+ T cells in Brucella infection.

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma and Induces Innate and Adaptive Memory Immune Mechanisms that Prevent Recurrence.

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME after treatment, as well as some variable changes in CD4+ and CD8+ effector (Tem) and central memory (Tem) lymphocytes in blood and spleen. After orthotopic challenge, CD8+ T-cells were cytotoxic, inducing apoptosis in N1-S1 cells; additionally, in contrast to post-treatment immune responses, CD4+ and CD8+ memory precursor effector cells (MPECs) and short-lived effector cells (SLECs) were present, while still including CD8+ CD161 NK cells, but not involving CD8+ CD314-NKG2D+ NKs. This immunity was N1-S1-specific and was sustained for at least 8 months. NPS vaccinates rats in vivo against HCC by activating innate and adaptive immune memory mechanisms that prevent HCC recurrence.

Early and late changes in natural killer cells in response to ledipasvir/sofosbuvir treatment.

Chronic hepatitis C virus (HCV) infection is characterized by dysregulated natural killer (NK) cell responses. NKs play a critical role in achieving sustained responses to interferon (IFN)‐α‐based therapy. Rapid sustained HCV‐RNA clearance is now achieved with direct‐acting antivirals (DAAs). Studies of patients receiving first‐wave DAAs suggest NK functional restoration. Here, we investigate the effect of mainstream DAA treatment on NKs. We collected a prospective cohort of male HCV genotype 1‐infected patients treated with ledipasvir/sofosbuvir (n = 22). Peripheral blood was obtained at treatment start, week 2 (W2), W4, W8, and W12 of treatment and 12 weeks posttreatment. Flow cytometry was used to characterize NK responses to therapy. Mean baseline viral load was 1.75 million IU/mL. All subjects rapidly cleared virus and remained HCV RNA‐negative posttreatment. No change was seen in total NK levels; however, the frequency of immature NKs (clusters of differentiation [CD]56bright) decreased by W2 and was maintained throughout the study. Phenotypic changes were evident by W2/W4, coincident with rapid viral clearance. At W2, T‐cell immunoglobulin and mucin‐domain containing‐3 and CD161 were significantly increased, returning to pretreatment levels by W12. Some changes were not evident until late (W12 or posttreatment). Down‐regulation of several activation markers, including NKp30 and tumor necrosis factor–related apoptosis‐inducing ligand, was observed at W12 and sustained posttreatment. No difference was observed in IFN‐γ production or cytokine‐mediated killing of NK‐sensitive cell line K562 posttreatment compared to pretreatment. Conclusion: Our phenotype data suggest transient activation followed by dampening of NK cell activity to pretreatment levels. The NK response to ledipasvir/sofosbuvir is not universal in a homogeneous patient cohort. More studies are needed to elucidate the roles of NK cells in IFN‐free regimens, which will have implications for protection from re‐infection and fibrosis progression. (Hepatology Communications 2018;2:364‐375)

Changes in natural killer cells and exhausted memory regulatory T Cells with corticosteroid therapy in acute autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an immune‐mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom‐AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3‐positive (FOXP3POS) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C‐X‐C motif) ligand 10. Chemokine secretion by cultured primary hepatocyte and biliary epithelial cells was measured by enzyme‐linked immunosorbent assay. Functional coculture assays with stimulated NK cells and Tregs were performed. CD161 ligand, lectin‐like transcript‐1 expression by intrahepatic immune cells was demonstrated with flow cytometry. Frequencies of NKbright cells declined with therapy (P < 0.001) and correlated with levels of alanine aminotransferase (P = 0.023). The Treg:NKbright ratio was lower pretreatment, and Tregs had an activated memory phenotype with high levels of CD39, cytotoxic T lymphocyte antigen 4, and FOXP3 but also high programmed death ligand 1, indicating exhaustion. Coculture experiments suggested the Tregs could not efficiently suppress interferon‐γ secretion by NK cells. Both Tregs and NK cells had high expression of liver infiltration and T helper 17 plasticity‐associated marker CD161 (P = 0.04). Pretreatment and CD161pos NK cells expressed high levels of perforin and granzyme B, consistent with an activated effector phenotype (P < 0.05). Lectin‐like transcript 1, a ligand for CD161, is expressed on intrahepatic B cells, monocytes, and neutrophils. Conclusion: Activated effector NK cells, which correlate with biochemical measurements of hepatitis, and exhausted memory Tregs are increased in the blood of patients with treatment‐naive AIH and decline with corticosteroid therapy. Inadequate regulation of NK cells by exhausted FOXP3pos Tregs may play a role in AIH pathogenesis and contribute to liver injury. (Hepatology Communications 2018;2:421‐436)

Functional and Phenotypic Changes of Natural Killer Cells in Whole Blood during Mycobacterium tuberculosis Infection and Disease.

Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity. However, major knowledge gaps exist on the contribution of NK cells in protection against Mtb infection or TB. We performed a cross-sectional assessment of NK cells phenotype and function in four distinct groups of individuals: TB cases pre-treatment (n = 20) and post-treatment (n = 19), and household contacts with positive (n = 9) or negative (n = 18) tuberculin skin test (TST). While NK cells frequencies were similar between all groups, significant decreases in interferon-γ expression and degranulation were observed in NK cells from TB cases pre-treatment compared to post-treatment. Conversely, CD57 expression, a marker of advanced NK cells differentiation, was significantly lower in cases post-treatment compared to pre-treatment. Finally, NKG2C, an activation and imprinted-NK memory marker, was significantly increased in TST+ (latently infected) compared to TB cases pre-treatment and TST− (uninfected) individuals. The results of this study provide valuable insights into the role of NK cells in Mtb infection and TB disease, demonstrating potential markers for distinguishing between infection states and monitoring of TB treatment response.

Mass Cytometry Analytical Approaches Reveal Cytokine-Induced Changes in Natural Killer Cells.

Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections and malignancies. To maintain cell viability and enhance antiviral and antitumor effects, NK cells are frequently treated with cytokines. Here they performed an extensive assessment of the effects of cytokines on the phenotype and function of human NK cells. They used cytometry by time-of-flight (CyTOF) to evaluate NK cell repertoire changes after stimulation with interleukin (IL)-2, IL-15 or a combination of IL-12/IL-15/IL-18. To analyze the high dimensional CyTOF data, they used several statistical and visualization tools, including viSNE (Visualization of t-Distributed Stochastic Neighbor Embedding), Citrus (Cluster identification, characterization, and regression), correspondence analysis, and the Friedman-Rafsky test. All three treatments (IL-2, IL-15, and IL-12/IL-15/IL-18) increase expression of CD56 and CD69. The effects of treatment with IL-2 and IL-15 are nearly indistinguishable and characterized principally by increased expression of surface markers including CD56, NKp30, NKp44, and increased expression of functional markers, such as perforin, granzyme B, and MIP-1β. The combination of IL-12/IL-15/IL-18 induces a profound shift in the repertoire structure, decreasing expression of CD16, CD57, CD8, NKp30, NKp46, and NKG2D, and dramatically increasing expression of IFN-γ. CyTOF provides insights into the effects of cytokines on the phenotype and function of NK cells, which could inform future research efforts and approaches to NK cell immunotherapy. There are several analytical approaches to CyTOF data, and the appropriate method should be carefully selected based on which aspect of the dataset is being explored. © 2016 International Clinical Cytometry Society.

Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia

The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-α and IFN-γ production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-α production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-α and IFN-γ production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival.

Characterization of age-related changes in natural killer cells during primary influenza infection in mice

The current investigation examined the importance of natural killer (NK) cells during the innate immune response to primary influenza infection in young and aged mice. Young (6–8 weeks) and aged (22 months) C57BL/6 mice were infected intranasally with influenza A virus, and NK cell-mediated cytotoxicity was determined in lung and spleen during the first 4 days of infection. Aged mice demonstrated both a decrease in influenza-inducible NK activity and a reduction in the percentage and number of NK1.1+ cells in response to primary influenza infection, relative to young mice. In order to further establish a role for NK cells in controlling influenza infection, young mice were depleted of NK cells in vivo by injecting rabbit anit-NK1.1 antibody 2 days and 1 day prior to influenza infection. Young mice depleted of NK cells exhibited increased weight loss and lung virus titers during the course of infection, compared to young mice infected with influenza virus. These data indicate that NK cell function is impaired in response to primary influenza infection in aged mice. More importantly, these results underscore the essential role of NK cells in controlling virus titers in lung during the early course of influenza infection, regardless of age.

Levels of circulating CD8+ T lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis

Background: Different exogenous and endogenous provocation factors such as mental stress are hypothesized as being relevant in the pathophysiology of atopic dermatitis (AD). Objective: The purpose of this study was to examine the effects of acute psychological stress on illness-specific immunologic parameters in AD. Patients with psoriasis and healthy volunteers were investigated in parallel. Methods: Patients with AD (n = 15), patients with psoriasis (n = 15), and control subjects (n = 15) were exposed to mental stress lasting 10 minutes (public speaking, mental arithmetic). In vitro analyses were done 1 hour before, immediately after, and 1 hour after stress exposure. Vital parameters (blood pressure, heart rate) and plasma noradrenaline concentrations were determined to prove the effects of mental stress on the individuals. Lymphocytes were phenotypically analyzed by flow cytometry. Results: The results indicate a higher ability of CD8+ T lymphocytes to react to stress, including the subpopulations of CD8+/CD11b+ T lymphocytes and eosinophils in patients with AD compared with healthy volunteers. The increases in the subpopulation of CD8+/CD11b+ T lymphocytes on psychological stress were higher in the patients with AD and psoriasis than in healthy control subjects. Significant stress-induced changes of natural killer cells were revealed for all 3 groups. Conclusion: The results suggest that psychological stress has different immunologic effects in patients with AD than in patients with psoriasis and healthy men. (J Allergy Clin Immunol 2001;107:171-7.)

THE EFFECTS OF HALF-MARATHON RUNNING ON NATURAL KILLER CELLS AND FREE RADICALS

106 The purpose of this study was to investigate the effects of half-marathon running (HMR) on natural killer cells and free radicals in blood. Eleven subjects (age=26.3 ± 4.5 yrs, ht=167 ± 6.7 cm, wt=56.5 ± 3.7Kg, ran 85.5 KM per week for 5.4 yrs on average) competed in the 1997 Taipei International Half-Marathon. Blood samples were taken before, and at 30 mins and 24 hrs after the race. The extent of changes in natural killer cells(NKcells), superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) and malondialdehyde (MDA), as well as creatine kinase (CK), and uric acid (UA) were measured. Results indicated that the number of natural killer cells in peripheral blood within 30 mins of HMR dramatically decreased and did not recover until 24 hrs. The level of uric acid rose significantly at 30 mins(from 6.75 to 8.55 mg/dL) but returned to a normal level at 24 hrs. Creatine kinase activity was twice the normal level at 30 mins (from 252 to 435 IU/L) after HMR, and over three times the normal level (to 875 IU/L) at 24 hrs. This may indicate that muscles were damaged. The MDA value is significantly higher at 24 hrs after HMR (from 2.34 to 2.79 U/ml). Conclusions: 1. HMR induced lipid peroxidation can possibly cause tissue damage; and 2. HMR can temporarily decrease immune function due to a decrease in the number of natural killer cells.

Changes in natural killer cells, the CD57CD8 subset, and related cytokines in healthy aging.

Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study. A significant increase with age was found in both the absolute counts and the proportions of CD3-CD(16+56)+, CD3+CD(16+56)+, CD57+CD8+, CD57+CD8(low)+, and CD57+CD8- cells, whereas the CD57+CD8(high)+ subset, which may represent the cytolytic T cell population more precisely, showed less change with age. Some evidence is also provided to suggest that these expanded NK cell populations are in an activated state. Soluble IL-2 receptor levels were also found to increase significantly with age and correlated with certain NK cell subsets. Although the functions of some of these subsets remain to be elucidated, their expansion in the elderly may represent a remodeling of the immune system with increasing age, with an increase in non-MHC-restricted cells perhaps compensating for the previously reported decline in T and B cells in the elderly. Alternatively, increased numbers of these cells may be a direct result of cytokine dysregulation or increased antigenic or neoplastic cell challenge.

Changes of natural killer cells during acute psychological stress.

Emotional stress is often followed by increased susceptibility to infections. One major role in the immediate immune response to infection is played by natural killer (NK) cells. This study was designed to establish whether acute psychological stress influences cellular immune functions and to elucidate the role of endocrine parameters as potent mediators of stress induced alterations of the immune system. Forty-five first-time tandem parachutists were examined continuously for their plasma concentrations of cortisol and catecholamines from 120 min before to 60 min after jumping. Lymphocyte subsets, NK activity, and ADCC were determined 2 hr before, immediately after, and 1 hr after jumping. There was a significant increase in sympathetic-adrenal hormones during (adrenaline, noradrenaline) and shortly after jumping (cortisol). Lymphocyte subsets and the functional capacity of NK cells revealed an increase immediately after jumping followed by a decrease significantly below starting values 1 hr later. These changes were significantly correlated to plasma concentrations of noradrenaline. Thus, quick mobilization of NK cells is suggested as one major mechanism for this effective adaptation of the immune system to stress situations.