Cell-mediated immunity in nutritional imbalance

Marked perturbations of cell-mediated immunity are observed in nutritional imbalance, both undernutrition and overnutrition. Individuals with protein-energy malnutrition show consistent impairment of cutaneous delayed hypersensitivity and a reduced number of circulating T lymphocytes. Variable changes in lymphocyte stimulation response in vitro to mitogens and antigens are seen. There is a relative increase in the number of "null" cells and high levels of leukocyte terminal deoxynucleotidyl transferase activity. These findings suggest impaired differentiation of T cell precursors, which may be the direct result of reduced thymic hormone activity. Alterations in the production of lymphokines are not consistent. Infants with intrauterine growth retardation show a marked and long-lasting deficit in cell-mediated immunity. Specific nutrient deficiencies vary in their ability to influence cell-mediated immunity and the mechanisms underlying the immunologic abnormalities. Among others, zinc and pyridoxine deficiencies are associated with marked immunodepression. Obesity also is associated with alterations in cell-mediated immune responses. This has been observed in man, in genetically obese mice, and in states of excess intake of lipids, vitamins, minerals, and a trace elements. Nutritional modulation of cellular immunity is an important determinant of morbidity in several systemic disorders.     

分枝杆菌制剂对小鼠的免疫调节作用的初步研究

探讨不同分枝杆菌制剂对小鼠的免疫调节作用。将C57BL/6小鼠,随机分成4组分别注射生理盐水、微黄分枝杆菌、草分枝杆菌和田鼠分枝杆菌制剂,每隔2周免疫一次。免疫2次后,小鼠取脾淋巴细胞体外培养,分别以PPD、PPDB刺激,用MTT法检测T淋巴细胞增殖情况;用酶联免疫斑点法(Enzyme-Linked ImmunoSpot assay,ELISpot)检测脾细胞分泌IFN-γ情况,分析各分枝杆菌制剂对小鼠免疫应答的影响。结果显示,与对照组相比,微黄分枝杆菌制剂和草分枝杆菌制剂免疫小鼠的T淋巴细胞增殖反应和脾细胞分泌IFN-γ均明显提高,其中微黄分枝杆菌组与对照组相比有显著性差异(p<0.01)。分枝杆菌制剂可促进小鼠免疫应答。     

Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin

Adoptive transfer of protective immunity to an aerogenic infection with the facultative intracellular bacterium Mycobacterium tuberculosis was mediated by a population of T cells acquired in the spleen of donor mice at the height of the primary cell-mediated immune response to an immunizing infection with M. bovis bacillus Calmette-Guerin. Successful adoptive immunotherapy was ablated by prior exposure of immune donor cells to ionizing radiation or by treatment of these cells with antibody raised against the Ly-2 marker. In contrast, however, the capacity of immune donor cells to passively transfer delayed-type hypersensitivity (DTH) responses to tuberculin was unaffected by prior treatment with antibody to Ly-2, but was completely ablated by treatment by antibody to Ly-1. These results indicate, that DTH and protective anti-tuberculous immunity are dissociable phenomena, mediated by separate populations of T lymphocytes.     

Effects of Sinusoidal 0.5 mT Magnetic Field on Leukocyte Adherence Inhibition

Exposure of T lymphocytes to an external 50 Hz and 0.5 mT magnetic field was investigated in vitro using leukocyte adherence inhibition (LAI) assay which is a measure of cell-mediated immunity. Adherence of T lymphocytes taken from healthy humans and from cancer patients before and after medical treatment is enhanced after 1 h exposure to the magnetic field. The experimental findings for the magnetic field 0.5 mT are compared with published data for 1 and 10 mT. The results are consistent with suggestions of magnetic field effects on immune function in humans.     

Factors contributing to the impairment of cellular immunity in cancer patients (author's transl)]

Factors contributing to the impairment of cell-mediated immunity in cancer patients were studied. Normal plasma enhanced the PHA-induced transformation of cancer lymphocytes. Cancer plasma suppressed the transformation of normal lymphocytes. The plasma factor(s), which might play an important role in the impairment of cell-mediated immunity in cancer, was further characterized to be heat-labile, being completely destroyed at 56 degrees C for 30 minutes. It was present on the surface of T lymphocytes, and was partially removable by digestion with 0.05% Bacto-trypsin. Moreover, the percentage of T cells in the peripheral blood of cancer patients was lower than that of normal as determined by the anti-human thymocyte serum cytotoxicity test and the spontaneous rosette forming test.     

Effect of testosterone on T cell-mediated immunity in two species of Mediterranean lacertid lizards

One of the primary assumptions of the immunocompetence handicap hypothesis is that testosterone has an immunosuppressive effect, but conflicting results have been reported in a variety of bird species concerning the effect of testosterone on the humoral and the T cell-mediated components of the immune system. The T cell-mediated component of the immune system is particularly important during the breeding season, because the likelihood of injury during sexual competition is high and T cell-mediated immunity is essential for healing wounds and resisting infection. In this study we examined the effect of experimentally increased levels of testosterone during breeding season on T cell-mediated immunity in male lizards of two Mediterranean lacertid species, Psammodromus algirus and Acanthodactylus erythrurus. The hormonal treatment significantly increased testosterone of the experimental individuals. T cell-mediated responses to phytohemagglutinin stimulation were significantly suppressed in testosterone-treated males of both species. Furthermore, there was a significant negative relationship between individual variability in T cell-mediated responsiveness and plasma testosterone concentration. The present study is the first to demonstrate testosterone-induced suppression of T cell-mediated immunity in lizards.     

Effects of purified soybean agglutinin on growth and immune function in rats

The objective of this study was to investigate the effect of purified soybean agglutinin on growth and immune function in rats. Thirty male Sprague-Dawley rats (77.8 +/- 2.6 g) were individually fed casein-cornstarch based diets containing 0, 0.05, 0.10, 0.15 or 0.20% soybean agglutinin (w/w) during a 20-day experiment. Growth declined linearly with increasing the concentration of soybean agglutinin (p < 0.05). The proliferation of lymphocytes in spleen, lymph nodes and blood decreased with an increase in dietary soybean agglutinin (p < 0.05). The concentrations of interleukin-2, interferon-gamma and tumor necrosis factor-alpha in plasma, spleen, and mesenteric lymph nodes as well as plasma concentrations of IgA, IgG and IgM also declined with increasing dose of soybean agglutinin (p < 0.05). The results show that dietary soybean agglutinin has negative effects on growth as well as both cell-mediated and humoral immune function of rats and appears to function in a dose-dependent manner.     

Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo

Cytotoxic T lymphocytes and natural killer cells are essential effectors of anti-tumor immune responses in vivo. Dendritic cells (DC) 'prime' tumor antigen-specific cytotoxic T lymphocytes; thus, we investigated whether DC might also trigger the innate, NK cell-mediated anti-tumor immunity. In mice with MHC class I-negative tumors, adoptively transferred- or Flt3 ligand-expanded DC promoted NK cell-dependent anti-tumor effects. In vitro studies demonstrated a cell-to-cell contact between DC and resting NK cells that resulted in a substantial increase in both NK cell cytolytic activity and IFN-gamma production. Thus, DC are involved in the interaction between innate and adaptive immune responses.     

The in vitro induction of T cells which mediate delayed-type hypersensitivity toward horse red blood cells.

Humoral and cell-mediated immunity to the antigen horse red blood cells (HRBC) were induced in vitro. The type of immune response induced, however, was dependent on the concentration of antigen present in the culture. Whereas intermediate concentrations of HRBC induced antibody-forming cells, high and low concentrations of HRBC induced T cells which, on transfer, mediated delayed-type hypersensitivity reactions. The inverse relationship between humoral and cell-mediated immunity often observed in vivo is, therefore, also evident when lymphocytes are stimulated with antigen in vitro.     

Trypanosoma cruzi immune evasion mediated by host cell-derived microvesicles

The innate immune system is the first mechanism of vertebrate defense against pathogen infection. In this study, we present evidence for a novel immune evasion mechanism of Trypanosoma cruzi, mediated by host cell plasma membrane-derived vesicles. We found that T. cruzi metacyclic trypomastigotes induced microvesicle release from blood cells early in infection. Upon their release, microvesicles formed a complex on the T. cruzi surface with the complement C3 convertase, leading to its stabilization and inhibition, and ultimately resulting in increased parasite survival. Furthermore, we found that TGF-β-bearing microvesicles released from monocytes and lymphocytes promoted rapid cell invasion by T. cruzi, which also contributed to parasites escaping the complement attack. In addition, in vivo infection with T. cruzi showed a rapid increase of microvesicle levels in mouse plasma, and infection with exogenous microvesicles resulted in increased T. cruzi parasitemia. Altogether, these data support a role for microvesicles contributing to T. cruzi evasion of innate immunity.     

Seasonal changes in the relationship between ornamentation and immune response in red jungle fowl

Resistance to disease is frequently suggested to be important in mate choice, but information about how immune status can be conveyed is lacking. During the breeding season, male red jungle fowl with large combs, a sexually selected trait, have lower levels of lymphocytes, but greater cell-mediated immunity, indicated by a cutaneous hypersensitivity response. Before the breeding season, however, both cell-mediated immunity and proportion of lymphocytes are positively correlated with comb length. Cell-mediated immunity is particularly important to jungle fowl during the breeding season, because the likelihood of injury during sexual competition is high and cell-mediated immunity is essential for healing wounds and resisting infection. This seasonal change in one aspect of immunity but not another suggests that the birds adaptively maintain certain immune system abilities, and that it can be misleading to use a single aspect of immune response in evaluating immunocompetence.     

Effect of staphylococcal toxin on lymphocyte receptors and function

Staphylococcal toxin at a concentration of 10(-3) inhibits in vitro the rosette-formation of lymphocytes, taken from healthy donors and patients with purulent septic diseases, with sheep and mouse red blood cells, changes the ratio of lymphocyte subpopulation, modifies the spontaneous antigen- and mitogen-dependent migration of leukocytes. The latter phenomenon is not linked with disturbances in the lymphokine-producing activity of lymphocytes, but results from changes in the migration properties of granulocytes.     

Cell-mediated amplification and down regulation of cytotoxic immune response against autologous human cancer

The cytotoxic host immune response toward autologous human cancer may be regulated by the immunoregulatory network. Here we show that helper T cells, cloned from peripheral blood lymphocytes that were sensitized in vitro against an autologous human malignant paraganglioma, proliferated against and made interleukin 2 when cocultured with the tumor-associated antigen in the presence of autologous accessory cells. Furthermore, the helper cell clones amplified cytotoxic immune response by peripheral blood lymphocytes against the paraganglioma cells in coculture with the blood lymphocytes and the paraganglioma cells. An autologous T cell line bearing suppressor phenotype, established from a lymph node that had been infiltrated with the paraganglioma tumor cells, in contrast to the helper cells, selectively suppressed the cytotoxic immune response by the blood lymphocytes against the paraganglioma cells in identical coculture. These results, therefore, demonstrate the existence of cell-mediated immunologic regulations of the cytotoxic immune response (concurrent amplification and suppression in the same host) against an autologous human tumor.     

Tight junction proteins expression and modulation in immune cells and multiple sclerosis

The tight junction proteins (TJPs) are major determinants of endothelial cells comprising physiological vascular barriers such as the blood–brain barrier, but little is known about their expression and role in immune cells. In this study we assessed TJP expression in human leukocyte subsets, their induction by immune activation and modulation associated with autoimmune disease states and therapies. A consistent expression of TJP complexes was detected in peripheral blood leukocytes (PBLs), predominantly in B and T lymphocytes and monocytes, whereas the in vitro application of various immune cell activators led to an increase of claudin 1 levels, yet not of claudin 5. Claudins 1 and 5 levels were elevated in PBLs of multiple sclerosis (MS) patients in relapse, relative to patients in remission, healthy controls and patients with other neurological disorders. Interestingly, claudin 1 protein levels were elevated also in PBLs of patients with type 1 diabetes (T1D). Following glucocorticoid treatment of MS patients in relapse, RNA levels of JAM3 and CLDN5 and claudin 5 protein levels in PBLs decreased. Furthermore, a correlation between CLDN5 pre‐treatment levels and clinical response phenotype to interferon‐β therapy was detected. Our findings indicate that higher levels of leukocyte claudins are associated with immune activation and specifically, increased levels of claudin 5 are associated with MS disease activity. This study highlights a potential role of leukocyte TJPs in physiological states, and autoimmunity and suggests they should be further evaluated as biomarkers for aberrant immune activity and response to therapy in immune‐mediated diseases such as MS.     

Gonadal hormone-dependent and -independent regulation of immune function by photoperiod in Siberian hamsters

Siberian hamsters (Phodopus sungorus) exhibit changes in reproductive and immune function in response to seasonal variations in day length. Exposure to short days induces gonadal regression and inhibits testosterone secretion. In parallel, short days enhance immune function: increasing leukocyte numbers and attenuating cytokine and behavioral responses to infection. We examined whether photoperiodic changes in leukocyte phenotypes and sickness behaviors are dependent on concurrent photoperiodic changes in gonadal function. Male hamsters were gonadectomized or sham-gonadectomized and either exposed to short days (9 h light/day; SD) or kept in their natal long-day (15 h light/day; LD) photoperiod for 10-13 wk. Blood samples were obtained for leukocyte enumeration, and hamsters were challenged with bacterial LPS, which induced behavioral (anorexia, reductions in nest building) and somatic (weight loss) sickness responses. Among gonad-intact hamsters, exposure to SD increased total and CD62L+ lymphocytes and CD3+ T lymphocytes in blood and significantly attenuated LPS-induced sickness responses. Independent of photoperiod, castration alone increased total and CD62L+ lymphocyte and CD3+ T lymphocyte numbers and attenuated somatic and anorexic sickness responses. Among castrated hamsters, SD exposure increased lymphocyte numbers and suppressed sickness behaviors. In castrated hamsters, the magnitude of most immunological effects of SD were diminished relative to those evident in gonad-intact hamsters. The SD phenotype in several measures of immunity can be instated via elimination of gonadal hormones alone; however, photoperiodic effects on immune function persist even in castrated hamsters. Thus, photoperiod affects the immune system and neural-immune interactions underlying sickness behaviors via gonadal hormone-dependent and -independent mechanisms.     

Effect of the inhibition of triiodothyronine (T3) production by thiamazole on the T3 and serotonin content of immune cells

Triiodothyronine (T3) and serotonin are present in the cells of immune system (blood, peritoneal and thymic lymphocytes, monocytes and granulocytes of the blood and peritoneal fluid, mast cells). In the present experiments the effect of thiamazole, an antithyroid drug was studied on the content of these two hormones in immune cells after one and two weeks of continuous treatment (by drinking water, containing 30 mg/100 ml thiamazole, ad libitum) in adult male rats, using flow cytometric and confocal microscopic analysis. In thymic lymphocytes both hormone contents significantly increased in both time points. A significant decrease of T3 was observed in peritoneal monocytes and granulocytes also in both time points, in peritoneal mast cells after one week and in blood lymphocytes after two weeks. Serotonin content in addition to the elevated thymic values (in both measurements) was significantly reduced in blood lymphocytes after two weeks. Confocal microscopy demonstrated heterogeneous cell populations with disparate hormone content and mostly diffuse localization The experiments call attention to the presence of T3 in the immune cells and to its variable concentration under the effect of a thyrostatic drug as well, as to the T3-serotonin relationship in the cells of the immune system.     

The immune response of viral hepatitis patients who use narcotic preparations

The characteristics of cell-mediated and humoral immunity were studied in 611 patients with different etiological forms of acute virus hepatitides (HB, HC, HB + C, HC + HBsAg). As the result of the systematic abuse of psychoactive preparations, introduced by intravenous injection, in 166 patients (27.2%) drug addiction developed, ehile 445 (72.8%) patients had no addiction. The study revealed that in drug users with HB the secondary T-cell immunodeficiency of the hyposuppressor type in combination with depression in B-cell-mediated immunity (a decrease in the absolute number of B lymphocytes) could be registered, and in patients having no drug addiction the secondary T-cell immunodeficiency characterized by a decrease in the content of T helpers simultaneously with the increased content of T suppressors and B lymphocytes.     

Leukocyte Activity Is Altered in a Ground Based Murine Model of Microgravity and Proton Radiation Exposure

Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU) model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure) result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and simulated microgravity effects on hematopoietic, specifically immune cells.     

Prolonged effect of stress (water and food deprivation) at weaning or in adult age on the triiodothyronine and histamine content of immune cells.

We used two days of total water and food deprivation as stress for female rats at weaning (three weeks old) and at adult age (two and a half months old). Triiodothyronine (T3) and histamine content of immune cells (lymphocytes, mast cells and monocyte-macrophage-granulocyte group in peritoneal fluid; lymphocytes, granulocytes and monocytes in blood; and lymphocytes in thymus) were studied three weeks after stress application using specific antibodies for flow cytometry and confocal microscopy. The stress at weaning increased T3 content of thymus lymphocytes. In case of adult T3, there was a cell type independent significant effect of stress, decreasing values in peritoneal fluid and slightly increasing effect in the blood. Histamine content of granulocytes was also significantly elevated. The experiments demonstrate that not only fetal or neonatal stress has long-lasting consequences, but also stress events in later periods of life in cells (organs) that are continuously differentiating. We will go on to discuss the importance of T3 and histamine in connection with stress and immunity.     

Memory T cells protect against Plasmodium vivax infection

Immunity induced by Plasmodium vivax infection leads to memory T cell recruitment activated during "relapse" or "re-infection". This study aims to characterise memory T cells in patients with acute or convalescent P. vivax infection. Lymphocytes were collected from patients infected by P. vivax, immune controls and naive controls. The proportion of immature memory T cells, expressing CD45RO(+)CD27(+), and mature cells lacking CD27 was assessed. A statistically significant increase in the median percentage of memory T cell subsets expressing CD4(+) was observed in material from patients with an acute infection compared with that from either naive or immune controls. The high percentage of memory T cells in infected patients was maintained until 60 days post treatment. The immune controls living in a malaria endemic area had a somewhat increased proportion of memory T cell subsets expressing CD8(+). An approximately three-fold increase of these cell types was shown in patients with an acute infection and the level persisted until 60 days post treatment. Phenotypic characterisation of the peripheral lymphocytes during acute infection revealed that a large fraction of the lymphocytes carried the gammadelta phenotypes suggesting a role for these cells in the early response against P. vivax. Very low levels of P. vivax specific antibody were found. This might suggest that cell-mediated immunity may play a greater role in the development of naturally acquired protection against P. vivax infection than humoral immunity. Our results provide further insight into the mechanism of cell-mediated immunity to P. vivax infection that could be important for the future development of a successful vaccine and anti-malarial drug designation.