Circulating leucocyte and lymphocyte subpopulations before and after intensive endurance exercise to exhaustion

Summary Seventeen healthy cyclists [age 20.8 (SD 4.8) years; body mass 68.3 (SD 7.7) kg; body fat, 11.4 (SD 2.6) %; height, 179.1 (SD 5.9) cm; 60.9 (SD 7.4) ml · kg^–1 · min^–1] conducted intensive endurance exercise to exhaustion (stress test, ST) on a cycle ergometer at 110% of their individual anaerobic threshold [Th_an,individua; exercise intensity, 3.97 (SD 0.6) W · kg^–1 ; duration, 23.9 (SD 8.3) min; maximal lactate concentration, 7.39 (SD 2.59) mmol · 1^–1]. The distribution of leucocyte subpopulations was measured flow cytometrically: before, immediately after (0), 5 (+5), 30 (+30) and 60 (+60) min after ST. The lymphocytes (0 min) and granulocytes (+60 min) were mainly responsible for the increase of leucocytes. Lymphocytes were significantly lower at +30 and + 60 min than before. CD3^–CD16/CD56⁺ (+480%) and CD8⁺-lymphocytes (+211%) increased at 0 min more than the other lymphocyte subpopulations (CD3+-cells, +100%; CD4⁺ cells, +56%; CD19⁺-cells, +64%). CD3^–CD16/CD56⁺-and CD8⁺-cells also were mainly responsible for the decreased values of lymphocytes at +30 min and +60 min compared to before. At 0 min naive CD8⁺ cells (CD45RA⁺, CD45RO^–) increased more than memory CD8⁺-cells (CD45RA^–, CD45RO⁺). Changes of naive and memory CD4⁺-cells did not differ. All lymphocyte subpopulations, in particular CD8⁺- and CD3^–CD16/CD56⁺-cells, decreased rapidly between 0 min and 5 min. We conclude that an intensive endurance exercise to exhaustion causes a mobilisation of lymphocytes, especially of natural killer cells (CD3^–CD16/CD56⁺) and naive, unprimed CD8+ cells (CD45RA⁺, CD45RO^–) which may be transported to injured muscles. The decreased cell numbers of the latter subpopulations are possibly one reason for the susceptibility to infections during the first hours after exercise. Furthermore, an exact definition of the intensity of exercise and times of taking blood is essential for comparing results describing cell parameters during or after exercise.     

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in na?ve T-helper (CD4+CD62L+; P<0.049) and na?ve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.     

Differential mobilization of leucocyte and lymphocyte subpopulations into the circulation during endurance exercise

Summary A total of 14 healthy subjects [means (SD): 27.6 (3.8) years; body mass 77.8 (6.6) kg; height 183 (6) cm] performed endurance exercise to exhaustion at 100% of the individual anaerobic threshold (Th_an) on a cycle ergometer (mean workload 207 (55) W; lactate concentrations 3.4 (1.2) mmol · l^–1; duration 83.8 (22.2) min, including 5 min at 50% of individual Th_an). Leucocyte subpopulations were measured by flow cytometry and catecholamines by radioimmunological methods. Blood samples were taken before and several times during exercise. Values were corrected for plasma volume changes and analysed using ANOVA for repeated measures. During the first 10 min of exercise, of all cell subpopulations the natural killer cells (CD3^–CD16/CD56+) increased the most (229%). Also CD3^÷CD16/CD56+ (84%), CD8^÷CD45RO^– (69%) cells, eosinophils (36%) and monocytes (62%) increased rapidly during thattime.CD3⁺, CD3⁺HLA-DR⁺, CD4⁺CD45RO⁺, CD4⁺CD45RO^–, CD8⁺CD45RO^÷ and CD19⁺ cells either did not increase or increased only slightly during exercise. Adrenaline and noradrenaline increased nearly linearly by 36% and 77% respectively at 10 min exercise. The increase of natural killer cells and heart rates between rest and 10 min of exercise correlated significantly (r=0.576,P=0.031). We conclude that natural killer cells, cytotoxic, non-MHC-restricted T-cells, monocytes and eosinophils are mobilized rapidly during the first minutes of endurance exercise. Both catecholamines and increased blood flow are likely to contribute this effect.     

Mobilization of circulating leucocyte and lymphocyte subpopulations during and after short,anaerobic exercise

Summary A group of 11 healthy athletes [age, 27.4 (SD 6.7) years; body mass, 75.3 (SD 9.2) kg; height, 182 (SD 8) cm; maximal oxygen uptake, 58.0 (SD 9.9) ml · kg^–1 · min^–1] conducted maximal exercise of 60-s duration on a cycle ergometer [mean exercise intensity, 520 (SD 72) W; maximal lactate concentration, 12.26 (SD 1.35) mmol · l^–1]. Adrenaline and noradrenaline, and leucocyte subpopulations were measured flow cytometrically at rest, after 5-min warming up at 50% of each individual's anaerobic threshold (followed by 5-min rest), immediately after (0 min), 15 min, 30 min, and 1, 2, 4 and 24 h after exercise. Granulocytes showed two increases, the first at 15 min and, after return to pre-exercise values, the second more than 2 h after exercise. Eosinophils also increased at 15 min but decreased below pre-exercise values 2 h after exercise. Total lymphocytes and monocytes had their maximal increases at 0 min. Out of all lymphocyte subpopulations CD3^–CD16/CD56⁺- and CD8S⁺ CD45RO^–-cells increased most and had their maximal cell counts at 0 min. The CD3⁺-, CD4⁺CD45RO⁺-, CD8⁺ CD45RO⁺-, and CD19⁺- increased at 0 min, but had their maximum at 15 min. During the hours after exercise CD3^– CD16/CD56⁺-, CD3⁺CD16/CD56⁺-, CD8⁺CD45RO⁺- and CD8⁺ CD45RO^–-cells were responsible for the lymphocytopenia. The CD3⁺- and CD3^– CD16/CD56⁺-cells were lower 24h after exercise than before exercise. Adrenaline and noradrenaline increased during exercise. In conclusion, short anaerobic exercise led to a sequential mobilization of leucocyte subpopulations. The rapid increase of natural killer cells and monocytes may have been due to increased blood flow and catecholamine concentrations. We interpreted from these results that those cells forming the first line of defence can be mobilized faster and disappear out of circulation more rapidly than all other cell populations.     

Effects of laboratory versus field exercise on leukocyte subsets and cell adhesion molecule expression in children

In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about these exercise responses during childhood and whether or not exercise in real-life activities of healthy children might influence immune responses. We compared laboratory exercise (10×2 min periods of heavy, constant intensity, cycle ergometer exercise with 1 min rests between exercise in nine subjects, aged 9–15 years) with field exercise (90 min soccer practice in nine different subjects, aged 9–11 years). Blood was sampled before both protocols, 5 min after the 30 min laboratory protocol, and 10–15 min after the 90 min field protocol. Both field and laboratory exercise protocols led to significant (P<0.05) increases in granulocytes, monocytes, and all lymphocyte subpopulations. The mean (SEM) increases were similar for the two protocols except for the significantly greater increase in laboratory compared with field protocols for natural killer cells [142 (39)% vs 12 (16)%, P<0.001] and monocytes [64 (22)% vs 32 (19)%, P<0.001]. Both protocols significantly influenced adhesion molecules (such as CD54) which have not been previously studied in children. However, the adhesion molecule CD8⁺CD62L^– increased to a significantly (P<0.001) greater extent in the laboratory [101 (25)%] versus field [34 (25)%] protocol. Finally, the density of CD62L on lymphocytes significantly decreased with laboratory exercise but showed no change in the field protocol [–20 (3)% vs –3 (3)%, P<0.001]. The rapid and substantial immune response in both laboratory and field protocols suggests that exercise stimulation of the immune system occurs commonly in the real lives of children and may play a role in their overall immune status. Electronic Publication     

NK细胞和NKT细胞在病毒性肝炎中的作用

NK细胞(Natural killer cells)和NKT细胞(Natural killer T cells)参与机体的天然免疫反应。NK细胞在肝炎病毒感染的早期免疫反应中起到重要作用,而慢性病毒性肝炎患者NK细胞功能降低。另外,动物实验显示NKT细胞可致肝组织损伤并能抑制肝炎病毒的复制。因此通过调节NK细胞和NKT细胞的功能治疗病毒性肝炎将有可能成为一种新的策略。     

The immune system and serum glutamine during a triathlon

This study examined the influence of a triathlon on the immune system and on serum amino acid concentrations. Eight male triathletes swam 2500 m, bicycled 81 km, and ran 19 km. The concentration of total serum amino acids decreased during the race, with the lowest values occurring 2 h postexercise. Similarly, serum glutamine concentration declined from 468 (SEM 24) (prerace) to 318 (SEM 20) μmoll⁻¹ (2 h postrace) and the natural killer (NK) and lymphokine activated killer (LAK) cell activities were suppressed 2 h postexercise (P < 0.05). Blood mononuclear cell proliferation decreased during exercise with the lowest value observed after running. The leucocyte concentration increased during and after exercise due to an increase in the concentration of neutrophils and monocytes. There was no significant change in lymphocyte concentration during or after the exercise. The plasma concentration of interleukin-6 did not change and the plasma concentration of interleukin-1β and tumor necrosis factor-α were below detection limits. The LAK cell cytotoxicity, but not NK cell activity or proliferative response, was significantly correlated with serum glutamine concentrations (r = 0.39,P < 0.01). This study confirms that prolonged endurance exercise results in changes in the cytotoxic function of the NK and LAK cells as well as the proliferative response. The time-course of changes in serum glutamine concentrations were best parallelled by changes in LAK cell activities.     

CD147 contains different bioactive epitopes involving the regulation of cell adhesion and lymphocyte activation

CD147 is a leukocyte surface molecule which belongs to the immunoglobulin superfamily. It is broadly expressed on various cell types and is a lymphocyte activation-associated molecule. In order to study the function of CD147, five CD147 monoclonal antibodies (mAbs) were generated: M6-2F9; M6-1D4; M6-1F3; M6-1B9; and M6-1E9. Biochemical characterizations and cross-blocking experiments indicated that M6-1B9 and M6-1E9 recognize the same or contiguous epitopes on CD147. By employing COS transfectants expressing CD147 membrane-distal domain (domain 1) and membrane-proximal domain (domain 2), mAbs M6-2F9, M6-1D4, M6-1B9, and M6-1E9 were shown to recognize epitopes located on domain 1 of the molecule. Functional studies indicated that engagement of CD147 by mAbs M6-1B9 and M6-1E9 strongly inhibited lymphocyte proliferation induced by a CD3 mAb. In contrast, mAbs M6-2F9, M6-1D4, and M6-1F3 induced U937 homotypic cell aggregation. The results indicate that CD147 contains at least two bioactive domains. Epitopes responsible for induction of cell aggregation are different from those regulating lymphocyte activation.     

Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood

NK cells and cytotoxic T lymphocytes can induce apoptosis in virus-infected and transformed target cells via the granule exocytosis pathway. The key components of the cytolytic granules are perforin and several serine esterases, termed granzymes. While the cellular distribution of human granzymes A (GrA) and B (GrB) has been well characterized much less is known about the expression pattern of human granzyme K (GrK). In this study GrA, GrB, and GrK expression was analyzed in human peripheral blood lymphocytes using flow cytometry. There was a distinct population of GrK expressing CD8+ T cells with a CD27+/CD28+/CCR5high/CCR7-/perforin-/low/IFN-gamma+ memory-like phenotype, while all CD56bright NK cells were also positive for GrK. In addition, GrK was also expressed in subpopulations of CD56+ T cells, CD4+ T cells, and TCRgammadelta+ T cells. In contrast, GrB was primarily expressed in CD56dim NK cells and differentiated memory CD8+ T cells with the CD27-/low/CD28-/low/CCR5-/low/CCR7-/CD11b+/perforinhigh phenotype. Only few CD8+ T cells expressed both GrB and GrK. GrA was found to be co-expressed in all GrB- and GrK-expressing T cells. Our findings suggest that granzyme expression during the differentiation process of memory CD8+ T cells might be as follows: GrA+/GrB-/GrK+ --> GrA+/GrB+/GrK+ --> GrA+/GrB+/GrK-.     

CD28 functions as an adhesion molecule and is involved in the regulation of human IgE synthesis

Activated T cells induce IgE switching in B cells via a combination of lymphokines and direct T:B cell contact. As CD28-deficient mice have reduced basal levels of IgG1 and IgG2a and diminished Ig class switching, we investigated whether the CD28/B7.1 (CD80) ligand pairing might also be involved in human IgE regulation. Co-incubation of an allergen-specific, human T cell clone with tonsillar B cells caused a marked up-regulation of CD28 expression, whereas, in contrast, CD45 RB expression was unaffected. To test whether blocking the CD28:B7.1 interaction affected IgE synthesis, a dialyzed anti-CD28 monoclonal antibody (mAb) was added to cultures containing tonsillar B cells, pre-activated T cell clones and interleukin-4. Anti-CD28 treatment caused a reproducible, dose-dependent inhibition of IgE, but not IgG synthesis that was accompanied by a visible decrease in cell aggregate formation. Conversely, an anti-B7.1 mAb had no effect in this system. The effect of blocking CD28-ligand interactions on lymphocyte adhesion was formally assessed on human T cell clones and B cell lines using dual intracellular staining and flow cytometry. Co-incubation with an anti-CD28 mAb, but not control IgG or anti-B7.1 mAb, resulted in a marked impairment of conjugate formation that correlated well with T cell surface expression of CD28. Using this system we found that an anti-CTLA-4 mAb but not an anti-B7.2 mAb inhibited T:B cell conjugate formation. Lastly, in addition to a direct effect of anti-CD28 mAb on conjugate formation, 14-day culture of T and B cells in the presence of anti-CD28 caused a marked decrease of ICAM-1 (CD54) expression on aggregated lymphocytes. In contrast, LFA-1 (CD18) expression was unaffected. We, therefore, conclude that the T cell co-stimulatory molecule CD28 is involved in the regulation of IgE synthesis in vitro. CD28 may act to a limited extent as an adhesion molecule, though apparently not by pairing with B7.1 or B7.2. It is more likely that ligation of CD28 under certain conditions modulates the expression of other T and B cell surface molecules.     

Exercise-induced alterations in natural killer cell number and function

To study the effects of exercise on natural killer (NK) cell number and activity (NKCA) healthy male (n = 32) and female (n = 32) subjects were randomly assigned to an exercise or control condition. Exercise involved a continuous incremental protocol consisting of cycling for three periods of 6 min at work rates corresponding to 55%, 70% and 85% peak oxygen uptake ( ). Blood samples were drawn at baseline, at 6 min, 12 min and 18 min during exercise, and at 2 h following completion of exercise. Relative to both baseline and control conditions, exercise resulted in an increase in the number of circulating lymphocytes. The proportion of T cells (CD3⁺) and B cells (CD19 ⁺) significantly decreased, and NK cells (CD3^–CD16⁺CD56⁺) increased throughout exercise. NKCA increased (P < 0.001) during the initial 6 min of exercise with no further changes observed, despite increases (P < 0.001) in the number and proportion of circulating NK cells during exercise at 70% and 85% . Plasma epinephrine and norepinephrine increased (P < 0.001) above baseline at 12 min and 18 min. The changes in NK cell number and function were independent of gender. The results indicate that short-duration low-intensity exercise can significantly increase NK cell number and activity. However, alterations in NK cell number are not accompanied by changes of a similar magnitude in NKCA.     

Effects of moderate endurance exercise and training on in vitro lymphocyte proliferation,interleukin-2 (IL-2) production,and IL-2 receptor expression

This study was designed to examine immunological responses to an acute bout of cycle ergometry exercise before and after moderate endurance training. Previously sedentary males were randomly assigned to matched training (n=9) or control (n=6) groups. Training comprised 12 weeks during which supervised cycle ergometer exercise took place [30 min at 65–70% of maximal oxygen intake , 4–5 days · week^–1]. An acute bout of exercise (60 min; 60% was performed initially and after the 12-week interval. Samples of peripheral venous blood were taken at rest, after 30 and 60 min of exercise, and at 30 and 120 min post-exercise. Training improved by an average of 20% (40.6 to 49.2 ml · kg^–1 · min^–1). Relative to baseline and control measures, the resting concentration of (CD3-CD16⁺/CD56⁺) natural killer (NK) cells increased by 22% (P<0.05). The resting count of total CD25⁺ [interleukin-2 receptor (IL-2R) chain] lymphocytes did not change following training, but dual staining analysis showed a 100% increase in the fraction of CD16⁺ CD25⁺ NK cells (P < 0.05). Likewise the resting CD122⁺ (IL-2R chain) lymphocyte count increased 35% after training, the greatest increases (44%) being in CD16⁺ CD122⁺ NK cells (P<0.05). Soluble IL-2R levels also increased 33% (P< 0.05) after training. Following acute exercise at the same relative intensity; trained individuals exhibited a larger increase in the NK cell count, reduced lymphocytopenia, and attenuation of exercise-induced suppression of lymphocyte proliferation and IL-2 production (P<0.05). In addition, smaller increases in CD4 and CD8 counts during exercise were noted, but with faster recovery post-exercise (P<0.05). Addition of recombinant IL-2 (rIL-2) to phytohemagglutinin-stimulated peripheral blood mononuclear cell cultures did not reverse exercise-induced suppression of cell proliferation, either before or after training. However, rIL-2 did augment the spontaneous blastogenesis of exercise and post-training samples relative to baseline (P < 0.05). We conclude that moderate endurance training is associated with sustained alterations in immune function, both at rest and when exercising. Further investigations are necessary to determine the impact on overall health and susceptibility to disease.     

Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma

Abstract. Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals (81 patients with liver disease and 42 healthy volunteers). The liver diseases included periportal fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T-cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease (P<0.01) in CD3 and CD4 T-cells, and a highly significant increase (P<0.001) in CD57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of liver cirrhosis and HCC.     

Developmental change in expression of highly polysialylated neural cell adhesion molecule in C-cells in rat thyroid gland

The expression of the neural cell adhesion molecule (NCAM), highly polysialylated NCAM, and Ecadherin was immunohistochemically studied in the calcitonin-producing cells (C-cells) of developing and adult rat thyroid glands of varying ages. In fetal and neonatal rat thyroids, almost all the C-cells displayed immunoreactivity for highly polysialylated NCAM, whereas most of the follicular cells were negative. The highly polysialylated NCAM-positive C-cells markedly decreased in number between 5 and 14 days after birth. From day 14 onward, immunoreactivity for highly polysialylated NCAM was almost negative in thyroid glands. On the other hand, the expression of immunoreactivity for NCAM peptide persisted in thyroidal C-cells throughout the life span. These results suggest that conversion of the highly polysialylated NCAM into a less sialylated form occurs in the thyroid C-cells between postnatal days 5 and 14. Intense immunoreactivity for E-cadherin was observed in the entire cell surfaces of all the C-cells and follicular cells in the rats of all ages tested. In the course of thyroid organogenesis, C-cells transiently form a cell mass, an ultimobranchial body, which is fated to disappear as the C-cells migrate diffusely into the thyroid. The duration of the polysialic acid expression in the C-cell surfaces appears to coincide with the period of C-cell migration. It is possible that the expression of highly polysialylated NCAM allows the C-cells to migrate into the thyroid by reducing the cell-to-cell adhesion of C-cells with adjacent C-cells and/or with the surrounding follicular cells.     

Cytokines and cell adhesion molecules associated with high-intensity eccentric exercise

Unaccustomed, eccentrically biased exercise induces trauma to muscle and/or connective tissue. Tissue damage activates an acute inflammatory response. Inflammation requires the effective interaction of different physiological and biological systems. Much of this is coordinated by the de novo synthesis of families of protein molecules, cytokines. The purpose of the present paper was to determine changes in blood levels of various cytokines in response to exercise-induced muscle damage that was effected using high-intensity eccentric exercise. Six healthy, untrained, college-age male subjects were required to perform the eccentric phase of a bench press and a leg curl (4 sets, 12 repetitions/set) at an intensity equivalent to 100% of their previously determined one-repetition maximum. Samples of blood were drawn at the following times: before exercise and 1.5, 6, 12, 24, 48, 72, 96, 120, and 144 h after exercise. These samples were analyzed for interleukins (IL): IL-lβ, IL-6, and IL-10; tumor necrosis factor-α; colony stimulating factors (CSF): granulocyte-CSF, macrophage-CSF, and GM-CSF; for cell adhesion molecules (CAM): P- and E-selectin, and intercellular cell adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1). Results were analyzed using a repeated-measures analysis of variance (P=0.05). Compared to baseline values, IL-1β was reduced (P=0.03) at 6, 24, and 96–144 h after exercise; IL-6 was elevated (P=0.01) at 12, 24, and 72 h after exercise; IL-10 was elevated (P=0.009) between 72 and 144 h after exercise; M-CSF was elevated (P=0.005) at 12 and 48–144 h after exercise; and P-selectin was reduced (P=0.01) between 24 and 144 h after exercise. It is concluded that when high-intensity eccentric exercise is compared to strenuous endurance exercise, post-exercise changes in cytokines do occur, but they are generally of a smaller magnitude, and occur at a later time period after the termination of exercise. Accepted: 28 December 1999     

开胸患者围手术期T细胞亚群及NK细胞的动态变化及意义

目的 :探讨开胸患者围手术期间细胞免疫功能的动态变化及其临床意义。方法 :应用流式细胞仪检测 4 5例开胸患者术前、术后 1、3、5及 7天的外周血T细胞亚群 (CD3、CD4、CD8、CD4 CD8)及NK细胞水平 ,并对 4 5例患者随机分组 ,比较纵隔、肺、食管贲门手术组围手术期T细胞亚群及NK细胞的变化。结果 :与术前相比开胸患者术后 1天CD4 CD8和术后 3天CD4降低。其中 ,纵隔肿瘤手术组术后 1天CD4 CD8和术后 3天CD4降低 ;肺部手术组合术后 1天及 7天CD8和术后 5天NK细胞降低 ,术后 5天CD3及术后 7天CD4 CD8升高 ;食管贲门手术组术后 1天CD4 CD8降低 ,术后 7天CD3及CD4升高。具有统计学意义 (P <0 0 5 )。结论 :开胸患者术后细胞免疫功能呈现受抑制状态而降低 ,主要出现在术后第 1～ 3天 ,术后第 5～ 7天开始恢复。因患者疾病种类及手术类型不同 ,细胞免疫功能受抑制持续的时间及恢复开始的时间不尽相同。食管贲门手术患者术后细胞免疫功能受抑严重且恢复较慢 ,肺部手术患者次之 ,纵隔肿瘤手术患者较轻。开胸患者术后 1周内应用抗菌素防治感染及适当免疫增强治疗是必要的。     

Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells

Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-α, IFN-β IFN-γ, IL-2 or tumor necrosis factor (TNF)-α and, unlike the induction of IFN-γ production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.     

TCR-independent cytokine stimulation induces non-MHC-restricted T cell activity and is negatively regulated by HLA class I

Recent evidence suggests that the functional status of T cells activated independently from their TCR differs substantially from classical MHC-restricted T cells. Here, we show that TCR-independent, short-term stimulation via the common gamma-chain of the IL-2/IL-15 receptor induces non-MHC-restricted cytotoxicity and sustained cytokine secretion in purified CD4+ or CD8+ T cells. NK-like cytotoxicity is directed against MHC class I-negative targets and can be inhibited by classical and non-classical HLA class I molecules. Known inhibitory receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are not involved. NK-like T cells display an activated phenotype and secrete various cytokines, including IFN-gamma, TNF-alpha, IL-5, IL-13 and MIP-1beta. Under normal conditions, HLA class I-mediated inhibition may function as a safety mechanism to prevent unbalanced cytokine production and effector killing mechanisms by T cells that were activated independently from their TCR. Non-MHC-restricted activity represents a functional status rather than a property of distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T cells may be relevant in immune responses against tumors showing aberrant MHC expression through their capacities of cytokine production and direct tumor cell eradication.     

Lack of stimulatory effect of dienogest on the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by endothelial cell as compared with other synthetic progestins

Objectives: Monocyte adhesion to endothelial cells is an important initial event at the onset of atherosclerosis. It is partially mediated by the expression of adhesion molecules on the endothelial cell surface. While estrogens inhibit the development of atherosclerosis, the effect of co-administered progestin remains controversial. We examined the effect of progestins on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. Methods: In HUVECs, mRNA expression of progesterone receptors (PRs) and androgen receptors (AR) was determined by RT-PCR. HUVECs were stimulated by interleukin-1β (IL-1β) for 24 h with or without various steroids, and then the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was semiquantified by ELISA. Results: In all preparations of HUVECs used in this study, RT-PCR confirmed mRNA expression of both isoforms of PR, PR-A and PR-B, as well as AR. Addition of progesterone (10⁻¹⁰–10⁻⁷ M) or dienogest (DNG) (10⁻¹⁰–10⁻⁸ M) did not affect IL-1β-stimulated ICAM-1 or VCAM-1 expression. In contrast, medroxyprogesterone acetate, norethindrone acetate and levonorgestrel (10⁻¹⁰–10⁻⁸ M) dose-dependently increased cell adhesion molecules. The progestin-induced increase was blocked by the concomitant addition of mifepristone, a PR antagonist, but not by hydroxyflutamide, an AR antagonist, indicating that the progestin stimulation was mediated predominantly via PR. Conclusions: These results suggest that DNG, unlike other synthetic progestins, lacks stimulation of cell adhesion molecules. For the prevention of atherosclerosis, estrogen in combination with DNG may be a suitable regimen in hormone replacement therapy in postmenopausal women.