Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.
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PMID:[Characteristics of immunologic test values in the elderly]. 933 53

We determined in 14 patients with pleural tuberculosis total lymphocyte count, T subsets and NK cells (CD56) in pleura and blood and it was found a preferential accumulation in pleura of CD3 T lymphocytes, TCR alpha beta, mainly CD4 subset, but not T or NK cells. In 5 pleuritis it was studied 40% of V beta TCR subfamilies in blood and pleura and in 2 pulmonary tuberculosis and one pleuritis all V beta and V alpha TCR subfamilies (trough PCR), without be observed a clear clonal expansion. It was not observed correlation among a) pleural and blood lymphocyte cellularity b) the amount of pleural effusion and the existence of lymphopenia or tuberculinic anergia c) levels of ADA and percentage of CD3 and CD4 cells in pleura. In 7 out 11 pleuritis a high expression of IL-2 receptor (CD25) was observed. In 24 patients with pleural and pulmonary tuberculosis there was not correlation between levels of SIL-2R and IL-6 and radiographic extension.
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PMID:[Lymphocyte activation in tuberculous pleuritis . Correlation with adenosine deaminase (ADA), peripheral blood lymphocytes, T cell receptor subfamilies, radiographic extension and levels of Il-6 and soluble Il-2 receptor]. 954 1

The purpose of this study was to evaluate in a randomized phase II trial the efficacy and toxicity of combination biochemotherapy compared with chemotherapy alone in patients with metastatic melanoma. Sixty-five patients with metastatic melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3), DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n = 35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s. (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9 MU (days 1-3). Evidence for immune activation was determined by flow cytometric analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up to six courses depending on response. The overall response rate of BCDT with IL-2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12-46%) with eight PRs; the median durations of response were 2.8 months and 2.5 months respectively. Sites of response were similar in both groups. There was no difference between the two groups in progression-free survival or overall survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant lymphopenia, evidence of immune activation was indicated by a significant rise in the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells) subsets, without any change in the percentage of CD4 or CD4 T-cell subsets. Toxicity assessment revealed a significantly higher incidence of severe thrombocytopenia in patients treated with combination chemotherapy than with chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu-like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous IL-2 and IFNalpha to BCDT chemotherapy in a randomized phase II trial resulted in immune activation but did not improve response rates in patients with metastatic melanoma, and indeed may increase some treatment-related toxicity.
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PMID:Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma. 957 34

The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial. Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg. Dose-dependent increases in serum IFN-gamma levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level. The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection. Rebound lymphocytosis, as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers were the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans.
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PMID:Immunological effects of interleukin 12 administered by bolus intravenous injection to patients with cancer. 991 97

Lymphopenia and immune deficiency are significant problems following allogeneic hematopoietic cell transplantation (HCT). It is largely assumed that delayed immune reconstruction is due to a profound decrease in thymus-dependent lymphopoiesis, especially in older patients, but apoptosis is also known to play a significant role in lymphocyte homeostasis. Peripheral T cells from patients who received HCT were studied for evidence of increased cell death. Spontaneous apoptosis was measured in CD3(+) T cells following a 24-hour incubation using 7-amino-actinomycin D in conjunction with the dual staining of cell surface antigens. Apoptosis was significantly greater among CD3(+) T cells taken from patients 19-23 days after transplantation (30.4% +/- 12.5%, P <.05), and 1 year after transplantation (9.7% +/- 2.8%, P <.05) compared with healthy controls (4.0% +/- 1.5%). Increased apoptosis occurred preferentially in HLA (human leukocyte antigen)-DR positive cells and in both CD3(+)/CD4(+) and CD3(+)/CD8(+) T-cell subsets, while CD56(+)/CD3(-) natural killer cells were relatively resistant to apoptosis. The extent of CD4(+) T-cell apoptosis was greater in patients with grade II-IV acute graft-versus-host disease (GVHD) (33. 9% +/- 11.3%) compared with grade 0-I GVHD (14.6 +/- 6.5%, P <.05). T-cell apoptosis was also greater in patients who received transplantations from HLA-mismatched donors (39.5% +/- 10.4%, P <. 05) or HLA-matched unrelated donors (32.1% +/- 11.4%, P <.05) compared with patients who received transplantations from HLA-identical siblings (19.6% +/- 6.7%). The intensity of apoptosis among CD4(+) T cells was significantly correlated with a lower CD4(+) T-cell count. Together, these observations suggest that activation of T cells in vivo, presumably by alloantigens, predisposes the cells to spontaneous apoptosis, and this phenomenon is associated with lymphopenia. Activation-induced T-cell apoptosis may contribute to delayed immune reconstitution following HCT. (Blood. 2000;95:3832-3839)
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PMID:Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. 1084 17

The objective of this study was to contribute to a better characterization of the immunological profile of idiopathic myelofibrosis (IM) at presentation by analysing the blood lymphocyte subsets and their possible correlations with other disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed in 31 IM patients, compared with those from 34 healthy individuals, and correlated with the patients' main clinical, hematological and bone marrow histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD 0.6) x 10(9)/L, versus 1.6 (SD 0.49) x 10(9)/L in controls (p = 0.0006), with 24 of the 31 patients (77.4%) showing lymphocytopenia (< 1.5 x 10(9)/L). IM patients had significantly lower counts of CD3, CD4, CD8, and CD3 -/ CD56+ cells, and significantly higher CD3 +/CD56 + lymphocyte counts. Although no significant differences were found between patients and controls with regard to CD19+/CD5+ cell counts, increased CD5 + B-cell lymphocytes were observed in three IM patients. In one of the latter patients, Ig gene rearrangement analysis of the heavy chain gene demonstrated such a subpopulation to be clonal, but the patient did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No correlation was found between the patients' blood lymphocyte counts and other disease features. We conclude that most IM patients have absolute lymphopenia, decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them show an increased CD5 + B-cell subpopulation.
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PMID:Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosis. 1096 69

The mechanism underlying immunosuppression after partial hepatectomy remains unclear. Hepatectomy induces lymphopenia, which is related to immunomodulation. The aim of this study was to determine whether peripheral blood lymphocytes (PBL) are susceptible to mitochondria-mediated apoptosis after hepatic resection. We compared the changes in mitochondrial membrane potential in lymphocytes from hepatectomized patients with metastatic liver tumor with the corresponding changes in lymphocytes from cholechystectomized patients, because changes in mitochondrial membrane potential have been reported to frequently occur during the early stages of apoptosis. Mitochondrial membrane potential, subpopulation, and apoptosis of lymphocytes were estimated with flow cytometry. Hepatectomy significantly (P<0.001) reduced postoperative mitochondrial membrane potential, while cholecystectomy slightly decreased it. Apoptosis of lymphocytes was increased on post-hepatectomy day, and this increase was correlated with the extent of mitochondrial membrane potential reduction. The major subset of lymphocytes with low mitochondrial membrane potential consisted of CD56(+) natural killer (NK) cells, and NK cell activity and cell counts significantly decreased after hepatectomy. Mitochondrial membrane potential of PBL was reduced after hepatectomy, and some lymphocytes underwent apoptosis through the mitochondrial pathway, which was one of the causes for lymphopenia. NK cells were more responsible for the decrease of mitochondrial membrane potential after hepatectomy than other lymphocytes, and the reduction in mitochondrial membrane potential in NK cells appeared to reflect modulation of the innate immune system.
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PMID:Mitochondrial membrane potential is reduced in peripheral natural killer cells following partial hepatectomy. 1203 5

The lymphocytopenia that occurs during the recovery stage of exercise may be a result of apoptosis through an increased expression of CD95, a loss of the complement regulatory proteins CD55 and CD59, or both. Trained subjects completed intensive, moderate, and downhill treadmill-running protocols. Blood lymphocytes isolated before, immediately after, 1h after, and 24h after each exercise test were assessed for markers of apoptosis (Annexin-V(+), HSP60(+)), and CD55, CD59, and CD95 expression by flow cytometry. Lymphocytopenia occurred 1h after intensive and downhill running exercise, but no changes in the percentage of Annexin-V + or HSP60 + lymphocytes were found. Numbers of CD95(+), CD55(dim), and CD59(dim) lymphocytes increased immediately after intensive and downhill exercise, which were attributed to the selective mobilization and subsequent efflux of CD8(+) and CD56(+) lymphocyte subsets. No differences were found between the intensive and downhill protocols. In conclusion, apoptosis of circulating lymphocytes does not appear to contribute to exercise-induced lymphocytopenia.
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PMID:Apoptosis does not contribute to the blood lymphocytopenia observed after intensive and downhill treadmill running in humans. 1798 5

Immunosuppression is a major side effect of cancer chemotherapy. The process of immune reconstitution can be dissimilar according to the nature of the disease, type and doses of drugs, and age of the patients. Recently, several studies have examined immune reconstitution in children and young adults after intensive chemotherapy for solid tumours or stem cell transplantation. The aim of the present study is to evaluate immune reconstitution (cellular and humoral) in children with acute lymphoblastic leukemia during the maintenance phase of therapy and to correlate between the complicating infections and the abnormalities in immune system during reconstitution. To achieve this goal, 36 children with acute lymphoblastic leukemia (24 females and 12 males) in the maintenance phase of therapy with 12 healthy children of matched age and sex served as a control group were recruited in this study. The patients were taken consecutively from the Hematology/Oncology Outpatient Clinic of Mansoura University Children's Hospital (MUCH). They were subjected to thorough history taking, clinical examination and laboratory investigations in the form of: complete blood count, serum creatinine, liver function tests and evaluation of the immune system by estimation of CD3, CD4, CD8, CD19 and CD56 (cellular immunity) by flow cytometry and immunoglobulins A, M and G (humoral immunity) at the first and the third month of maintenance therapy. The results of the study documented presence and persistence of leucopenia and lymphopenia during maintenance therapy with decreased medians of CD3, CD4 and CD8 from the first to the third month of therapy and in comparison to the control group. The other markers CD19, CD56, IgA, IgM, IgG and CD4/CD8 ratio showed increasing median from the first to the third month of therapy. Also we detect a significant correlation between infection and CD19 and serum IgM at the first month and between infection and CD19, IgM and CD4/CD8 ratio at the third month of therapy. In conclusion, persistent immunosuppression is documented in children with acute lymphoblastic leukemia during maintenance therapy. Reconstitution of B lymphocytes and Natural killer cells occurs early while T cell reconstitution shows delayed recovery of both T helper and T suppressor cells. Immunosupression during maintenance therapy has no major clinical impact in terms of increased incidence or severity of systemic infections.
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PMID:Immune reconstitution during maintenance therapy in children with acute lymphoblastic leukemia, relation to co-existing infection. 1879 45

Regulatory T cells (Treg) are important regulators of anti-cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3(+); CD3(-)CD16(+)CD56(+); CD4(+); CD8(+); CD19(+); CD4(+)CD45RA(+)) with emphasis on Treg counts (CD3(+)CD4(+)CD25(+)), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; alpha-1-antitrypsin [AAT]; Cyfra 21-1; C-reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8(+) cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4(+) cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21-1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 x 10(12)/l versus 4.45 x 10(12)/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy.
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PMID:Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck. 1918 42


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