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Lymphocyte subsets in acute rheumatic fever and rheumatic heart disease.

Lymphocyte subsets in 53 patients with acute rheumatic fever and 78 patients with chronic rheumatic heart disease were compared with 20 normal control subjects and 39 patients suffering from uncomplicated streptococcal pharyngitis to obtain information about the pathogenesis of the disease. Twenty patients with rheumatic fever were followed for 24 weeks to evaluate changes occurring over the course of the disease. Total leukocyte and lymphocyte counts were increased in patients with rheumatic fever and to a lesser extent in those with rheumatic heart disease, when compared with controls. The difference between the two groups was significant. Patients with acute rheumatic fever had an increased number of B cells and a smaller increase in total T and T-helper-inducer (CD-4) cells. The proportion of B cells increased, while that of T-suppressor-cytotoxic (CD-8) cells fell. An increased number and proportion of B cells was also seen in patients with rheumatic heart disease. Total T and T-helper lymphocyte percentages and numbers were significantly higher in patients with rheumatic fever compared with those of patients with rheumatic heart disease. Follow-up studies at 6, 12, and 24 weeks revealed no significant differences from the entry point studies, although there was a trend toward reduction in the degree of derangement from normal values. Patients with uncomplicated streptococcal pharyngitis, however, did not show perturbations in the T-cell and T-subset counts. Our study suggests that the immunoregulatory defect in acute rheumatic fever is characterized by a relative reduction of suppressor T cells with an absolute increase in helper T cells and B cells, resulting in an increased cellular as well as humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Specific IgG1 and IgG2 antibody and lymphocyte subset levels in naturally Leishmania infantum-infected treated and untreated dogs.

Peripheral blood lymphocyte subpopulations and specific IgG1 and IgG2 antibody levels were studied in 14 dogs naturally infected with Leishmania infantum using flow cytometry and ELISA. Six dogs (Group 1) were asymptomatic, and received no treatment. Samples from this group were collected from D0 to D180. The other eight dogs (Group 2) showed clinical symptoms, and were treated with Glucantime (from D0 to D40), with samples being collected from D0 to D90. Twenty-two healthy dogs were used as a control group (Group 3). The results demonstrated changes in the lymphocyte subsets, as well as a decrease in humoral and cellular immunity, in the infected dogs. Analysis of the B-cell populations of Groups 1 and 2 showed a striking reduction in the number of CD21+ cells. There was also a reduction in the CD5+, CD4+ and CD8+ T-cell populations. Drug therapy was found to partly restore the lost immunity, essentially the cell-mediated immunity. Both IgG1- and IgG2- specific antibodies were detected in sera from the fourteen infected dogs, but the IgG2 subclass appeared to be predominant. A significant decrease in the level of IgG2 antibodies was observed in treated and untreated dogs.

Animals↗

Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra.

Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no association between cytokine release and bone mass or loss assessed over 2 yrs. The only exception was a weak estrogen-independent correlation between basal IL-1ra secretion and bone loss (r = -0.21, p < 0.05). Flow cytometry did not confirm a relationship between CD4/CD8 T-cell ratios and bone density or loss, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p < 0.01) similar to that found in patients with established osteoporosis, indicating that these adherent mononuclear cells may be important in the pathophysiology of post-menopausal bone loss. The possibility that IL-1ra acts as an independent bone-sparing factor unrelated to estrogen withdrawal warrants further investigation. In conclusion, ERT maintains bone without affecting the release of the IL-1 family of cytokines in whole blood cultures.

Bone Density↗

Effect of local sympathectomy on 24-h changes in mitogenic responses and lymphocyte subset populations in rat submaxillary lymph nodes during the preclinical phase of Freund's adjuvant arthritis.

Wistar male rats received a bilateral superior cervical ganglionectomy or sham-operation and 10 days later were injected with Freund's complete adjuvant or its vehicle. Two days later, rats were killed at six different time intervals throughout a 24-h cycle. The mitogenic effect of lipopolysaccharide (LPS) and concanavalin A (Con A) and the relative size of lymphocyte subset populations were measured in submaxillary lymph nodes. Cells from sympathectomized lymph nodes showed a lower response to Con A. Freund's adjuvant injection decreased amplitude of daily rhythm in Con A response, an effect prevented by denervation. Generally, ganglionectomy increased Con A response at the early phase of arthritis. Acrophases for Con A and LPS effect occurred at early afternoon and did not change after ganglionectomy. Administration of Freund's adjuvant caused a 10-h advance in acrophase of LPS mitogenic activity, an effect prevented by ganglionectomy. Significant 24-h rhythms were observed in relative size of lymph node B and T cells. Denervation augmented amplitude of rhythm in B cells in adjuvant's vehicle-injected rats. As far as T lymphocyte subsets, acrophases occurred at the afternoon (CD4(+) and CD4(+)-CD8(+) cell types) or at night (CD8(+) cell types). Immunization augmented amplitude of 24-h rhythms in CD4(+)-CD8(+) cells regardless of innervation whereas denervation counteracted the suppression of daily rhythm in CD8(+) cells seen in arthritis. The results indicate that some of the changes seen in 24-h organization of immune responses in lymph nodes at an early phase of arthritis are modified by severing the local sympathetic nerves.

Animals↗

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy.

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.

Aged↗

Correlations between change in disease activity and changes in peripheral blood lymphocyte subsets in patients with juvenile dermatomyositis.

OBJECTIVE: To investigate whether changes in peripheral blood lymphocytes correlate with changes in disease activity in juvenile dermatomyositis (JDM). METHODS: Clinical changes in disease expression measured by a disease activity score were correlated with changes in percentages of peripheral blood lymphocyte subsets. RESULTS: Changes in the percentage of peripheral blood CD19 positive lymphocytes (B cells) correlated with changes in disease activity (Spearman rank coefficients = 0.47, p = 0.02). There were no significant correlations in disease activity with changes of T cell subsets or the T cell activation markers CD25 or DR. CONCLUSION: Change in the percentage of peripheral blood B cells correlates with change in disease activity in patients with JDM. This variable may be of use as an indicator of immunologic activity and response to therapy.

Adolescent↗

Effect of neonatal treatment with a gonadotropin releasing hormone antagonist on developmental changes in circulating lymphocyte subsets: a longitudinal study in male rhesus monkeys.

We have examined changes in circulating lymphocyte subsets from the neonatal period until adulthood (4 months until 5.5 years of age) in male rhesus monkeys, and the impact of neonatal treatment with a GnRH antagonist (Ant) or Ant and androgen (Ant/And) on these parameters. Absolute numbers of lymphocytes, B cells, total T lymphocytes, and CD4+ T cells decreased, neutrophils increased, and CD8+ T cells did not change with age. WBC counts increased between 4 mo and 2 years of age and then fell to neonatal levels over the next two years. The decline of CD4 + T cells in association with stable CD8+ T cell levels resulted in an age-related decrease in the CD4+/CD8+ T cell ratio. At 4 months of age, WBC's, lymphocytes, total T cells, CD8+ T cells and B cells were lower in Ant- and Ant/And-treated animals compared to controls. With the exception of WBC counts, these values had normalized by 2 years of age. Reduced WBC levels in treated animals persisted through adulthood. CD4+ T cell levels tended to be lower in Ant-treated and higher in Ant/And-treated animals than in controls at 4 months of age. CD4+ T cells remained lower in Ant- than in Ant/And-treated animals at most ages. The higher CD4 + T cell counts in Ant/And-treated animals resulted in an elevated CD4 + /CD8 + T cell ratio that persisted until the onset of year 5. During years 5 and 6, seasonal fluctuations in WBC's and neutrophils were observed with counts being higher in the breeding (fall) than in the nonbreeding (summer) season. The data document that developmental changes in circulating immune cells in the rhesus monkey are qualitatively similar to those reported in humans, and provide further evidence that neonatal treatment of male rhesus monkeys with Ant or Ant/And may alter early programming of the immune system.

Aging↗

T lymphocyte subsets in the skin lesions of patients with leprosy.

Lymphocyte subsets in the tissues of fourteen patients with leprosy were studied using monoclonal antibodies and a modified immunoperoxidase technic. Two immunohistologic patterns were observed. In tuberculoid leprosy, helper-inducer cells were present among the aggregates of mononuclear phagocytes (epithelioid cells), but the suppressor-cytotoxic cells were predominantly in the lymphocytic mantle surrounding the epithelioid cell aggregates. In reversal reaction and lepromatous tissues, the helper-inducer and the suppressor-cytotoxic cells were both distributed among the mononuclear phagocytes (histiocytes). In tuberculoid specimens the Langerhans cells of the epidermis were increased in number as compared to lepromatous and normal tissues. The technic used appears to be of value in studying some of the cellular components of the immune response in situ.

Antibodies, Monoclonal↗

Quantitation of lymphocyte subsets by immunofluorescence flow cytometry in idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) is a disease in which immune aberration has been postulated but not confirmed. The frequency of lymphocyte subsets was evaluated in 22 patients with IDC and in 22 blood bank control subjects, using monoclonal antibodies to cell surface markers to allow cell sorting by immunofluorescence flow cytometry. Eighteen patients with heart failure from other causes were also studied. Functional correlations were also made for the natural killer cell subset. Total T-cell frequency, determined with antihuman T (Hybritech), was similar in IDC and control groups: mean 73 +/- 12% in IDC patients and 70 +/- 9% in control subjects. B-cell frequency, determined with antihuman Ia (Hybritech), was also similar: 36 +/- 11% in IDC patients and 31 +/- 10% in control subjects. Helper T-cell frequency, identified by OKT4 (Ortho), averaged 47 +/- 11% in IDC and 44 +/- 8% in control subjects (difference not significant). Suppressor/cytotoxic T-cell frequency, established by OKT8, was the same: 28 +/- 8% in IDC and 30 +/- 7% in control subjects, although relative deficiency in suppressor functional activity has been reported in IDC. Helper to suppressor (OKT4/8) ratios, aberrant in many autoimmune diseases, did not differ significantly (IDC 1.9 +/- 0.8, control 1.5 +/- 0.6). Lymphocyte subsets and OKT4/8 ratio were also similar between IDC and heart failure patients. Natural killer cell frequencies, estimated using 2 antibodies (antihuman Leu-7 and Leu-11, Becton-Dickinson) were the same (9.3 +/- 4.9% in IDC patients, 9.0 +/- 4.5% in control subjects, Leu-7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Research of the relation between the type of asthenia of the spleen and kidney and platelet associated antibodies and T-lymphocyte subsets in idiopathic thrombocytopenic purpura].

Idiopathic thrombocytopenic purpura (ITP) is a kind of disease associated with immunity. At present a great quantity of study on ITP has been made on humoral and cellular immunity. But there are few reports about the relationship between the types based on the differential diagnosis of TCM and immune rationale of ITP. In order to deeply explore the relationship between the types based on differential diagnosis of TCM and immune rationale of ITP., the authors measured PAIg and T lymphocyte subsets of 34 ITP patients of asthenia of both Spleen and Kidney. The value of PAIgG increased in both types of Spleen failing to control blood (SFCB) and deficiency of Spleen-yin and Kidney -yin (DSYKY), and the value of PAIgG of the type of DSYKY was significantly higher than that of SFCB (P less than 0.01). OKT3, OKT4/OKT8 of the type of SFCB remarkably decreased (P less than 0.05), OKT4, OKT4/OKT8 of DSYKY also remarkably decreased (P less than 0.001), while OKT8 significantly increased (P less than 0.001). The above results suggested that the type of DSYKY has more serious immune dysfunction than the type of SFCB, and the types of SFCB and DSYKY has close relationship with PAIg T lymphocyte subsets.

Adolescent↗

A longitudinal study of lymphocyte subsets in a cohort of cats naturally-infected with feline immunodeficiency virus.

Despite the potential of feline immunodeficiency virus (FIV) as an animal model for human immunodeficiency virus (HIV) studies, the long term effects of naturally-occurring infection have not been determined. HIV infection causes an ongoing deterioration in immune function which directly correlates with disease, in particular acquired immunodeficiency syndrome (AIDS). However, it is not known whether FIV-induced immunosuppression is progressive or related to the clinical condition. This study examined changes in lymphocyte subset numbers of serial samples, taken from cohorts of FIV-positive and FIV-negative cats over and 18-month period. FIV-positive cats were clinically staged as asymptomatic carriers (AC) or cats with AIDS-related complex (ARC), and FIV-negative cats matched and staged on the basis of similar diseases. During the course of the study, 4 FIV-positive cats developed AIDS, classed as the terminal stage of infection. There were no significant differences in the mean absolute numbers of any lymphocyte subset between the onset (t0) and the completion (t18) of the study. Similarly there were no significant changes in subset numbers during the 18 months preceding the development of AIDS. While the study period was brief and the sample sizes small, it is postulated that FIV infection in Australia may not necessarily cause progressive immunodeficiency and that FIV-induced immunosuppression (as measured by subset analysis) may not be well correlated with the clinical status of the infected cat.

Animals↗

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival.

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-alpha and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients.

Adult↗

In vivo modulation of the circulating lymphocyte subsets and monocytes by androgen.

Androgens influence some immunological processes, including alternation of the number and function of the circulating lymphocytes and monocytes. In the present study, the effects of three different doses of testosterone on the numbers and percentages of the peripheral blood cells were investigated; the lymphocyte subsets were determined and the proliferation of lymphocyte was detected. Groups of Sprague-Dawley rats were treated with 0.5, 2.5, 12.5 mg/kg or only vehicle, respectively. Compared with controls, the results of complete blood counts showed that the absolute and relative numbers of monocytes decreased. The lymphocyte subpopulations determined by flow cytometry indicated an increase in CD8+ T cells, whereas the CD3+, CD4+ and CD4+CD8+ T cells remained unchanged. Thus, the immunoregulatory index (CD4+/CD8+ ratio) decreased. The proliferative activities determined by MTT assay were down-regulated. In conclusion, the immunosuppressive effects of testosterone may be attributed to a decline in number of monocytes, CD4+/CD8+ ratio and proliferative activities together with an increase of CD8+ T cells in Sprague-Dawley rats.

Animals↗

A comprehensive study on neurobehavior, neurotransmitters and lymphocyte subsets alteration of Chinese manganese welding workers.

The neurotoxicity of manganese has been demonstrated by many researches. But few reports have been found on its immunotoxicity in manganese-exposed workers. Here we selected welding workers (aged 34 years) as Mn-exposed subjects. They have been exposed to manganese for 16 years. The control group was from a flour plant. The average concentrations of Mn, Cd, Fe and Ni in work place were 138.40 +/- 11.60 microg/m3, 581.40 +/- 45.32 microg/m3, 3.84 +/- 0.53 microg/m3 and 12.64 +/- 2.80 ng/m3, respectively. Blood Mn (4.84 mug/dl) of welding workers was higher than that of the control group (1.92 microg/dl). Neurobehavioral core test battery (NCTB) recommended by WHO was conducted on the subjects and found that the scores of negative emotions, such as confusion-bewilderment, depression-dejection, fatigue-inertia, and tension-anxiety, were higher in welding workers. Visual simple reaction time and the fast simple reaction time were shorter than that of the control group. The numbers of digital span, forward digital span, backward digital span and digital symbol decreased in welding workers compared with control group. Monoamine neurotransmitters and their metabolism substances in urine were tested by HPLC-ultraviolet. NE, E, MHPG, HVA, DA, DOPAC and 5-HT in the urine of Mn-exposed group had no significant changes while 5-HIAA in Mn-exposed group had significantly decreased compared with that of the control group. Lymphocyte subsets of the subjects were determined by Flow Cytometer. CD3+ T cell, CD4+CD8- T cell, CD4-CD8+ T cell, CD4+CD45RO- "virgin" lymphocytes, CD4+CD45RO+ "memory" lymphocytes, and CD3-CD19+ B cell had no significant changes compared with the control group. The results showed that long-term exposure to manganese in welding might have adverse effects on mood state, neurobehavior, and peripheral neurotransmitters. However, they had no effects on lymphocyte subsets parameters.

Adult↗

Direct immunomagnetic quantification of lymphocyte subsets in blood.

A method is described where superparamagnetic polymer microspheres coated with monoclonal antibodies (MoAb) are used for the direct and fast quantification of the absolute number of cells of various lymphocyte subsets in blood. Blood samples were incubated with microspheres coated with a subset specific MoAb. Using a magnet the microsphere-rosetted cells were isolated and washed. Following lysis of the cell walls to detach the microspheres, the cell nuclei were stained with acridine orange and counted in a haemocytometer using an immunofluorescence microscope. With MoAb specific for CD2, CD4, CD8 and CD19, reproducible absolute counts of the corresponding lymphocyte subsets were obtained which correlated closely with those obtained by an indirect quantification method.

Cell Separation↗

[T-lymphocyte subsets of peripheral blood monocytes and their ability to form T-cell colony in breast tumor].

T-lymphocyte subsets and their ability to form T-lymphocyte colony were studied in 29 patients with breast cancer, 13 patients with benign breast diseases, and 28 normal females. Cellular immunity was found suppressed in breast cancer patients with an abnormally elevated percentage of OKT8. There were a reversed ratio of T4/T8, low T-cell proliferation, and some immunity-suppressing factors in the peripheral blood. These abnormalities were most evident in stage III breast cancer patients. The ratio of T4/T8 increased significantly and the colony formation of T cells greatly improved (P less than 0.001) 5-6 months after radical mastectomy in 7 patients, It is suggested that immune suppression of tumor is strengthened after surgery.

Adult↗

Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed type 1 (insulin-dependent) diabetes mellitus.

Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset less than 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 +/- 8.5% versus 70.7 +/- 8.0%), helper/inducer cells (OKT4+: 33.8 +/- 7.0% versus 47.1 +/- 8.3%), suppressor/cytotoxic cells (OKT8+: 18.5 +/- 7.3% versus 32 +/- 6.8%) and monocytes (OKM1+: 11.5 +/- 3.8% versus 19.9 +/- 5.2%) (p less than 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p less than 0.01-0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2 +/- 1.3 versus 1.5 +/- 0.3; p less than 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Out data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.

Adolescent↗

Lymphocyte subsets in patients with idiopathic thrombocytopenic purpura during high-dose gamma globulin therapy.

Peripheral lymphocyte subsets (OKT3+, OKT4+, OKT8+) were studied by monoclonal antibodies in 10 patients with chronic idiopathic thrombocytopenic purpura (ITP), before and after high-dose intravenous gamma globulin therapy at a daily dose of 0.4 g/kg/body weight for 5 consecutive days followed by several boosters every 10-15 days. A stable increase of platelet count was obtained in 5 patients, whereas the other 5 showed a transient improvement of platelet count but then became refractory to the treatment. Phenotypic analysis of T cell subsets showed a decrease of the OKT4+/OKT8+ ratio following therapy, with non change in the percentage of OKT3+ cells. A significant decrease of lymphocyte count and platelet associated IgG was shown in 80% of our patients. These data suggest the possible long term efficacy of repeated iv IgG inchronic ITP patients through a mechanism of specific enhancement of suppressor T cell function.

Adolescent↗