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PubMed1995

FIV vaccine studies. II. Clinical findings, hematological changes and kinetics of blood lymphocyte subsets.

Five groups of cats were vaccinated with different recombinant feline immunodeficiency virus (FIV) SU vaccines expressed either in Escherichia coli or in the Baculovirus system. In Part I of this series, we described the humoral immune response and outcome of intraperitoneal FIV challenge exposure. Additionally, all cats were monitored for clinical and hematological changes and the course of blood lymphocyte subsets. These results are described in this present paper. A great increase of antibodies was found after vaccination with different recombinant FIV antigens, which did not protect the cats from intraperitoneal FIV challenge infection. This observation was paralleled by an increase of eosinophils during vaccination which was even more pronounced after challenge infection. After FIV challenge, infection lymphadenopathy, gingivitis, pharyngitis, changes in total leukocytes and neutrophils and a decrease in the CD4+:CD8+ ratio were found in cats of all groups and were considered as a sign of the FIV infection taking place, independent of vaccination. The following observations suggest that in these cats a TH2-like immune response was elicited: the high counts of eosinophils, the nature of antigen and adjuvant (aluminium hydroxide) and the high amounts of antigens used for immunization. Clearly, this type of immune response did not protect the animals from intraperitoneal FIV challenge infection.

Animals↗
PubMed1992

Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients.

Cellular aspects of the immunomodulating activity of the galactoside-specific lectin from mistletoe (ML-1) were investigated in 10 cancer patients. Regular subcutaneous injections (4 weeks) of the optimal dosis of ML-1 (1 ng per kg body weight, twice a week) yielded notable increases in the apparent numbers of certain lymphocyte subsets [pan T cells; helper T cells; natural killer (NK) cells] which are generally believed to be involved in antitumor immunity. Moreover, ML-1 administration resulted in an increased level of expression of interleukin (IL)2 receptors on lymphatic cells, an indicator of cellular activation. In vitro, the exposure of human lymphocytes to ML-1 resulted in an enhanced expression of receptors for IL-2 (T cells) and HLA-DQ (B cells), which similarly substantiated the capacity of ML-1 to affect immunological parameters within the host defense system. Thorough clinical trials are now required to assess any impact of the application of the lectin on the course of the disease.

Biomarkers↗
PubMed1994

Flow cytometric determination of leukocytes and lymphocyte subsets in thrombocytapheresis products.

To determine the nature of the leukocyte contamination of platelet concentrates we developed a method to identify the immunophenotype of the leukocytes in platelet concentrates. Flow cytometry is ideally suited for this type of rare event detection. Using LDS-751, Forward Scatter and Side Scatter and a modified lysis protocol we were able to discriminate leukocytes from platelets and erythrocytes leaving 2 fluorescent channels free for immunophenotypic analyses. With this protocol we analyzed the leukocyte content and lymphocyte subset distribution pattern of peripheral blood and of the resulting thrombocytapheresis product of 40 blood donors at our institute. We found that the leukocyte content of the platelet concentrate existed almost purely (median 97%, 95-99%) of lymphocytes and monocytes (median 2%, 0-5%), granulocytes were < 1%. Within the lymphocyte population in thrombocytapheresis products the distribution of CD3, CD19, CD4, CD8, CD57, CD5, HLA-DR and gamma/delta T cells did not differ significantly from the corresponding distribution in the peripheral blood of the donors. We conclude that this flow cytometric method can be used as quality control to monitor leukocyte content and lymphocyte distribution of platelet concentrates.

Adult↗
PubMed1996

[Measurement of the plasma transforming growth factor-beta 1 (TGF-beta 1) level in patients of gastric carcinoma--compared with the serum IAP level and the lymphocyte subsets (CD3, CD4, CD8)].

We evaluated the clinical significance of the plasma TGF-beta 1 by enzyme-linked immunosorbent assay (ELISA) in 40 patients with gastric carcinoma before operation who were hospitalized at our department between August 1992 and March 1993. Moreover, we examined the correlation of the immunosuppressive acidic protein (IAP) in the serum with the plasma TGF-beta 1 level. The lymphocyte subsets were analyzed with monoclonal antibodies (CD3, CD4, CD8) and compared with the plasma TGF-beta 1 level. Results 1) The plasma TGF-beta 1 was significantly high in patients with advanced stage of gastric carcinoma (with respect to the depth invasion) and poorly differentiated adenocarcinoma (histological type) (p < 0.01). When the carcinoma was macroscopically found to be advanced, TGF-beta 1 was higher in the invasive type than in the noninvasive type (p < 0.05). 2) We found a significant correlation between the plasma TGF-beta 1 and IAP in the serum (n = 25, r = 0.677, p < 0.01). 3) The lymphocyte fraction of CD3, CD4 was decreased in patients with a high level of TGF-beta 1, and was related with the plasma TGF-beta 1 level. Thus, TGF-beta 1 was presumed to be deeply associated with in the growth and progression of gastric carcinoma and related to systemic immunosuppressive reaction.

CD3 Complex↗
PubMed2001

Microemulsion cyclosporin formulation, in contrast to the old formulation, widens the T lymphocyte subsets differences between stable and acute rejection of kidney transplants.

BACKGROUND: The new cyclosporin (CsA) formulation, Neoral, has different pharmacokinetics compared with Sandimmune (SIM). Larger area under the curve (AUC) values with equivalent trough blood values are reached when Neoral is administered at equivalent doses to SIM. Previously, we showed a great diagnostic reliability when using cytofluorometric analysis from fine-needle aspiration biopsy (FNAB) samples. We investigated possible changes brought about by Neoral on lymphocyte subsets and the repercussions on the activation score cut-off for acute rejection, defined under SIM treatment. METHODS: Of 63 patients that received SIM, 40 remained rejection-free and 23 suffered one episode of rejection. Of 52 patients that received Neoral, 38 remained rejection-free. Peripheral blood lymphocytes (PBL) and lymphocytes from FNAB taken on days 7 and 14 post-transplantation and on the first day of acute rejection were analysed by flow cytometry. RESULTS: Trough blood CsA levels were not different between SIM and Neoral treatments. Among rejection-free patients, a significant down-regulation of CD3DR and of CD8DR expression on both graft-infiltrating lymphocytes (GIL) and PBL, and significant up-regulation of naïve T cells on GIL were observed with Neoral. These changes were followed by a significant down-regulation of the activation score with Neoral. Conversely, within the acute rejection group, the activation score was significantly higher with Neoral than with SIM. The activation score performed equally well in Neoral transplants compared with what we had reported with SIM. CONCLUSIONS: Our study indicates that Neoral elicits stronger immunosuppressive effects in stable patients, which eventually should translate into better clinical efficiency. However, when acute rejection supervenes, the treatment breakthrough seems stronger with Neoral. Cytofluorometric studies from FNAB samples showed that diagnostic reliability was maintained at a high level under Neoral therapy.

Antigens, CD↗
PubMed1994

Lymphocyte subsets in thymus and peripheral lymphoid tissues of aging and diabetic NOD mice.

The nonobese diabetic (NOD) mouse spontaneously develops insulin dependent diabetes mellitus. The disease is associated with a leucocytic infiltration of the pancreatic islets of Langerhans and it is believed that during the development of autoimmune diabetes, the insulin-secreting islet beta-cells are destroyed by autoreactive T lymphocytes. We investigated the alteration of lymphocyte subsets in central and peripheral lymphoid organs of NOD female mice with increasing age beginning before the onset of insulitis and ending well after the onset of diabetes. The spleen, inguinal and pancreatic lymph nodes all increased in cell number, especially after the onset of insulitis (8 weeks), and all decreased after the onset of diabetes. Flow cytometric studies showed a widening of the visible side scatter profile of female NOD lymph node cells which coincided with the initiation of insulitis. Anti-CD4 and anti-CD8 double staining of thymocytes revealed a large increase in the double negative population and a corresponding decrease in the double positive population, but this occurred long after the onset of diabetes. Generally, there was an increase in the CD4:CD8 ratio in the peripheral lymphoid organs during the onset of insulitis which was largely due to an increase in the CD4 T cell population while the ratio decreased after the onset of diabetes. In the spleen this was mostly due to an increase in CD8 T cells. The pancreatic lymph nodes, which theoretically might reflect what is happening in the pancreas, showed an unexpected decrease in overall cell number and a decrease in T-cells (especially CD4 T cells), while B cells were increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2001

Flow-cytometric analysis of lymphocyte subsets and mCD14 expression in patients with various periodontitis categories.

BACKGROUND: Membrane-bound CD14 (mCD14) is expressed mainly on circulating monocytes and tissue macrophages. It is one of the receptors, which act at the recognition of lipopolysaccharides by host cells. Periodontopathic bacteria result in activation of cellular and humoral immune responses. AIM: The aim of the present study was to analyze the peripheral blood mCD14 concentrations as well as cell surface markers of lymphocyte subsets in periodontitis patients of various categories. MATERIALS AND METHODS: Peripheral blood samples were obtained from 22 early onset periodontitis (EOP), 10 adult periodontitis (AP) patients and 13 systemically and periodontally healthy control subjects. Three-color flow cytometry and a panel of relevant monoclonal antibodies were used to determine the percent expression of various cell surface markers on peripheral blood mononuclear cells (PBMCs). The results were tested statistically by one-way variance analysis and Newman Keuls test. RESULTS: No significant difference was observed between the study groups with regard to the relative counts of B-cells, T-cells, T-helper, T-cytotoxic/suppressor, activated T-cells and natural killer cells. EOP patients expressed significantly lower level of interleukin-2 receptor (IL-2R) when compared with AP patients (6.08% and 19.3% respectively) (p<0.05). The level of mCD14 in EOP patients (7.18%) was lower than that of AP patients (9.3%) and the control subjects (9.2%), but the differences were not statistically significant. CONCLUSIONS: The low level of IL-2R in the EOP group may be interpreted as an insufficient responsiveness to the periodontopathogens, which may be ultimately related with the more severe tissue destruction. Though not significant, the reduced expression of mCD14 in EOP group may also be related with the immune system deficiencies in these patients.

Adolescent↗
PubMed1989

Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, T19+ and B cells) through fetal lymph nodes.

The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, T19, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas T19+, CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of T19+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells.

Animals↗
PubMed2000

Migration of helper T-lymphocyte subsets into inflamed tissues.

The localization of lymphocytes to specific tissues is a finely regulated event that has key implications in the development of chronic allergic inflammation that is associated with allergic rhinitis, atopic dermatitis, and asthma. Key players in the tissue localization of lymphocytes and other allergic effector cells include cellular adhesion molecules and chemokines. The expression or activation pattern of these proinflammatory mediators appears to depend, in part, on the local cytokine milieu. For instance, the T(H)1 phenotype is associated with the upregulation of intercellular adhesion molecule-1 and RANTES, whereas the T(H)2 phenotype is associated with the upregulation of vascular cell adhesion molecule and P-selectin. Notably, the recruitment of certain cell populations, such as eosinophils (hallmark of chronic allergic inflammation), into inflamed tissue sites is dependent on the preferential expression of adhesion molecules, chemokines, and associated receptors. The potential mechanisms that underlie cell migration into inflamed tissue as currently understood are reviewed.

Cell Movement↗
PubMed1996

Alteration of peripheral blood lymphocyte subsets in essential hypertension.

OBJECTIVE: To assess lymphocytic subpopulation by labelled monoclonal antibody technique in a small group of patients with untreated essential hypertension (EH) and to detect any alteration with control of blood pressure. DESIGN: Prospective study with phenotypic estimation of lymphocytes at presentation and a minimum of two weeks after the control of blood pressure. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, normotensive controls (n = 10); group 2, mild to moderate essential hypertension (n = 10); group 3, severe (accelerated/malignant) hypertension (n = 10). All the secondary causes of hypertension were ruled out by a thorough history, physical examination and appropriate radiological and biochemical investigations. TESTS: Venous blood samples, taken at entry and a minimum of two weeks after control of blood pressure, were analyzed by alkaline phosphatase antialkaline phosphatase (APAAP) antibody technique for CD4, CD3, CD8 and CD22. Peripheral lymphocytes were separated and cocultured with phytohemagglutinin (PHA) for 72 h and assayed for CD25 by the APAAP technique. MAIN RESULTS: In untreated patients with EH (groups 2 and 3), there was a significant down regulation of CD3, and CD4 lymphocytes whereas the proportion of mature CD22 cells increased. In group 3 there was a significant down regulation of CD25 with PHA stimulation. A negative correlation was observed between CD25 and diastolic pressure upon pooling the results of groups 2 and 3. No significant alteration in these parameters was observed following control of blood pressure with drugs for up to two weeks. CONCLUSION: In this small group of patients with untreated EH, a significant alteration in the lymphocytic repertoire was observed. Whether this will be found in large groups of hypertensives remains to be seen.

Adult↗
PubMed1999

Requirement for multiple lymphocyte subsets in protection by a live attenuated vaccine against retroviral infection.

Infection by live attenuated retroviruses provides excellent protection from challenge with pathogenic viruses in several animal models, but little is known about which immune effectors are necessary for protection. We examined this using adoptive transfer experiments in the Friend virus mouse model. Transfers of immune spleen cells into naive mice conferred complete protection, and transfers of purified lymphocyte subsets demonstrated that this effect required complex immune responses involving CD4+ and CD8+ T cells and also B cells. In addition, passive immunization experiments demonstrated that antibodies alone reduced virus loads but did not prevent infection. These findings may have implications for retroviral vaccine design in general.

Adoptive Transfer↗
PubMed1986

Changes in peripheral lymphocyte subsets during radiotherapy for lung cancer patients.

In order to better understand the immunologic effects of irradiation, blood levels of lymphocyte subsets were sequentially monitored in 37 patients before and during irradiation treatment for lung cancer. During irradiation, the peripheral blood levels of each T cell subgroup, OKT3-reactive (OKT3+), OKT4+, OKT8+ and OKT11+ lymphocytes showed similar radiosensitivity. No selective depletion of either OKT4+ or OKT8+ lymphocytes was seen. The levels of OKT6+ and OKT9+ lymphocytes were different depending on the case. At the end of irradiation, the percent of lymphocytes bearing the OKT10 antigen increased significantly. As to OKM1+ and OKIa1+ lymphocytes, the levels were almost consistent but showed a rather big standard deviation.

Aged↗
PubMed1985

Isolation of highly purified lymphocyte subsets for functional studies by means of an indirect rosette technique.

An indirect rosette assay, utilizing ox erythrocytes (RBC) coupled with rabbit anti-mouse IgG and lymphocytes sensitized with monoclonal mouse antibodies against membrane markers, was used for purification of lymphocyte subsets that were functionally intact. Either peripheral blood mononuclear cells (PBMC) or T lymphocytes isolated by sheep RBC rosetting could be used as starting material for obtaining pure T-cell subsets (T4 or T8). The following steps of the method were evaluated: the procedure of coupling rabbit anti-mouse IgG to ox RBC via the CrCl3 method, the experimental conditions for specific rosetting, and the use of Percoll for the separation of rosettes from the non-rosetting cells. Under optimal experimental conditions the recovery of positively selected cells was 45-55% of the cells originally present in the PBMC. The purity of these cells reached a value of more than 95%, whereas the contamination of the depleted fraction was less than 3%. The functional integrity, manifesting itself as proliferation after mitogen stimulation and as regulatory influences on in vitro Ig synthesis, appeared to be unimpaired. The described technique may be applied to the purification of various cell subpopulations for functional studies, provided monoclonal antibodies against membrane antigens are available.

Animals↗
PubMed2000

Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes.

Wistar male rats were injected s.c. with melatonin (30 microg) or vehicle, 1 h before lights off, for 11 days. Ten days after beginning melatonin treatment, rats received Freund's complete adjuvant or its vehicle s.c., and after 2 days, they were sacrificed at six different time intervals throughout a 24-h cycle. The mitogenic effect of lipopolysaccharide (LPS) and concanavalin A (Con A), the activity of ornithine decarboxylase (ODC) and the relative size of lymphocyte subset populations were measured in submaxillary lymph nodes. In control rats, the mitogenic effects of LPS and Con A and ODC activity peaked during the afternoon. Injection of Freund's adjuvant induced a 10-h shift in the diurnal rhythm of the mitogenic effect of LPS to attain maximal values at night. Melatonin pretreatment blunted the daily variations in the mitogenic activity of Con A or LPS and, when given to Freund's adjuvant-injected rats, augmented mesor and amplitude of diurnal rhythm in ODC activity. Maxima in B cell number occurred at night whereas those of T and B-T cell number occurred during the afternoon. During the early phase of immunization tested, the number of B cells augmented and the amplitude of its diurnal rhythmicity increased both after immunization and following melatonin pretreatment. Maxima of 24-h rhythms in CD4+ and CD4+/CD8+ cell populations occurred during the afternoon while those of CD8+ cells occurred at late night. Melatonin significantly augmented CD4+ cell number and decreased CD8+ cell number; it therefore augmented the CD4+:CD8+ ratio. The results suggest that pretreatment with a pharmacological dose of melatonin exerts immunomodulating effects at an early, preclinical, phase of Freund's adjuvant-induced arthritis in rats.

Analysis of Variance↗
PubMed2004

Human tonsillar tissue block cultures differ from autologous tonsillar cell suspension cultures in lymphocyte subset activation and cytokine gene expression.

Lymphoid tissues cultured either as tissue blocks or as cell suspensions are used to study the behaviour of immune cells within their habitat. The preservation of tissue structures in tissue blocks, which is considered to be a major advantage, has been poorly defined. We characterised the morphological evolution of tissue cultures from human palatine tonsils and compared their lymphocyte subsets and the constitutive cytokine gene expression to those in autologous tonsillar single-cell suspension cultures over time, and after adding cyclosporin A (CsA) to mimic the situation in individuals treated with immunosuppressive drugs. Density and morphology of follicles were conserved up to 4 days, during which tissue cultures exhibited similar cell viability as suspension cultures, but a significantly less frequent increase of CD95 expression in T cells, smaller variation of the proportion of CD4(+) cells and better CD21(+)/CD23(-) B-cell survival. Treatment with cyclosporin A at higher concentrations resulted in superior histologic preservation of lymphoid tissue structures and seemed to further prevent the expression of CD95 by CD3(+) cells and the activation in tissue culture of CD21(+) cells. Constitutive gene expression levels of the stromal cytokines interleukin (IL)-1beta and interleukin-6 in tissue culture were significantly higher than those in suspension cultures. These results suggest that tonsillar tissue cultures preserve their structure only for a limited time, during which they more closely reflect processes in vivo, including a state of iatrogenic immunosuppression, than do their cell suspension counterparts.

Antigens, CD↗
PubMed2002

Acute psychological stress simultaneously alters hormone levels, recruitment of lymphocyte subsets, and production of reactive oxygen species.

Very little is known about the effects of acute psychological stress on the production of reactive oxygen species (ROS) by human phagocytic cells and the interplay between subjectively perceived stress, mediating hormones, variations in the number of peripheral leukocytes and ROS production. We measured psychological reactions, cardiovascular parameters, plasma catecholamines, plasma prolactin and cortisol as well as peripheral lymphocyte subsets in 13 experimental subjects undergoing a brief psychological stressor, and production of ROS, as indicated by chemiluminescence (CL), in stressed subjects and in healthy controls. The stressor elevated anger (p<0.01) and cardiovascular activation (p<0.01). There were significant changes in plasma levels of cortisol (p<0.01) and prolactin (p<0.001). During psychological stress natural killer (NK) cells (p<0.01) and CD8/CD38 cells (p<0.05) increased and returned to baseline only 25 minutes later. Significant changes in the number of naive CD4+/CD45RA+ (p<0.01) and antigen-experienced CD8+/CD45RO+ T cells (p<0.05) occurred. Subjects with stronger cardiovascular reaction showed higher stress-related plasma levels of norepinephrine (p<0.05) and were mainly responsible for the increase in NK cells. We observed a significantly reduced production of ROS following the stress test (p<0.05). Our results show that psychological stress is expressed simultaneously on psychological, hormonal and immunological levels of the organism. We show the existence of a circadian rhythm leading to a pronounced increase in CL during the morning hours. This first study taking this circadian rhythm in account revealed a significant suppressive effect of stress on ROS production.

Adult↗
PubMed1997

Peripheral blood lymphocyte subsets in fleece rot-resistant and -susceptible sheep.

OBJECTIVE: To compare haematological values and lymphocyte phenotypes in the peripheral blood of fleece rot-resistant and -susceptible sheep. PROCEDURE: Experiments were conducted on 2- and 3-year-old Merino rams, flock 1 (17 rams) and flock 2 (32 rams), respectively. Within each flock, individual rams were classified as fleece rot-resistant or -susceptible, based on established criteria. Total and differential white cell counts, and indirect fluorescent antibody tests specific for B cells and T cells were performed on all sheep. The concentration of various subsets of circulating lymphocytes was then determined in each sheep. RESULTS: There were no significant differences between fleece rot-resistant and -susceptible sheep from either flock in the mean total or differential white cell counts. However, fleece rot-resistant rams in flock 1 did have a significantly higher concentration of circulating SBU-T1+ cells than fleece rot-susceptible rams from the same flock. No such difference was noted in the rams from flock 2. While all rams in flock 1 were free of clinical fleece rot, 24 rams in flock 2 (comprising all 17 fleece rot-susceptible and 7 of 15 fleece rot-resistant animals) had clinical signs of the disease. Fleece rot-free rams in this flock (irrespective of their classification as fleece rot-resistant or -susceptible) had significantly higher concentrations of circulating SBU-T1+ cells compared with fleece rot-affected animals. They also had significantly higher concentrations of circulating B cells, and total lymphocytes. CONCLUSIONS: An examination of peripheral blood lymphocyte subsets in fleece rot-resistant and -susceptible sheep revealed a possible association between resistance to fleece rot and the concentration of circulating SBU-T1+ cells.

Animals↗
PubMed1994

Streptococcal toxic shock-like syndrome: evidence of superantigen activity and its effects on T lymphocyte subsets in vivo.

Toxic shock-like syndrome is a serious complication of invasive streptococcal disease. The syndrome is believed to be the consequence of exposure to exotoxins produced by the infecting organisms which behave as superantigens. We describe two patients who fulfilled clinical criteria for this syndrome, one of whom died. Streptococci isolated from both patients were found to produce a mitogen specific for the V beta 2+ T lymphocyte subset in vitro, which had the characteristics of a superantigen. The phenotype and function of lymphocytes collected from both patients during the acute phase of their illness demonstrated a marked reduction in circulating CD4+ ('helper') and CD45RA+ ('naive') T lymphocytes expressing the V beta 2 chain, and an increase of those expressing CD8, CD45RO and the V beta 2 chain. This effect resolved within 4 weeks in the patient who survived. Proliferation assays demonstrated no T cell anergy in either patient. Stimulation of lymphocytes by superantigen in these clinical situations does not appear to cause permanent deletion of T cell subsets, as has been observed in animal models.

CD4-Positive T-Lymphocytes↗