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)

Peripheral blood lymphocytes from 17 patients with autism were separated on a Ficoll-Hypaque density gradient. Patients had normal numbers of T and B cells and T cell subsets. Although CD4:CD8 ratios were normal for the whole group (2.09 +/- 0.97), 6 patients had elevated ratios (> 2.2) and 5 had decreased ratios (< 1.5). Mitogen-induced proliferation (concanavalin-A and phytohemagglutinin) was normal as was the autologous mixed lymphocyte reaction for the whole group. There was an abnormally increased percentage of DR+ (activated) T lymphocytes in 11 patients. With increasing age percentage of DR+ lymphocytes decreased. No patient had interleukin-2 (IL-2) receptor+ cells. Similar investigations performed on blood samples from 8 girls with Rett syndrome produced normal results. 11 of 17 autistic patients had an abnormally increased percentage of DR+ but not IL-2 receptor+ lymphocytes suggesting 'incomplete' activation, a finding which is seen in autoimmune diseases. The decrease in activated cells with increasing age suggests that there may be an autoimmune process which is more active earlier in life in a subset of autistics.
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PMID:Lymphocyte function in autism and Rett syndrome. 812 18

Recombinant human interleukin-2 (IL-2) was administered by the intravenous (i.v.) or intralymphatic (i.l.) route to 14 patients with advanced malignancy. IL-2 was given in doses of 600,000 IU/kg or 1,050,000 IU/kg daily x 5. Thoracic duct (TD) catheters were placed, and both TD lymphocytes (TDL) and peripheral blood lymphocytes (PBL) were studied. Five of eight patients at the 600,000 IU/kg dose experienced grade III toxicity as did five of six patients at the 1,050,000 IU/kg dose. Two episodes of grade IV toxicity were seen at the higher dose. The i.l. and i.v. routes had a similar toxicity profile excepting lymphangitis/pedal infection, seen only with i.l. administration. One partial response was seen in a patient with renal cell carcinoma. Lymphopenia was seen early in therapy, with lymphocytosis by day 6. Lymphoid yield of the TD catheter fell early in therapy, then increased over baseline by the end of treatment. Intralymphatic administration resulted in a prolonged serum t1/2 and lower serum levels than did i.v. administration, but resulted in higher TD levels. Antibodies against IL-2 were ubiquitous but had no clear effects. Lymphocyte trafficking studies suggested that IL-2 affected lymphocyte redistribution to liver, spleen, bone marrow, and lymph nodes. NK activity and phenotype and LAK activity increased in response to IL-2, with no advantage for TDL. Tumor necrosis factor-alpha and gamma-interferon levels increased sporadically with treatment. The i.l. route offered no advantage over the i.v. route, and TDL offered no advantage over PBL.
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PMID:A comparative study of intravenous versus intralymphatic interleukin-2, with assessment of effects of interleukin-2 on both peripheral blood and thoracic-duct lymph. 813 47

Twenty patients (6 females and 14 males), age range 36-70 years-old, with metastatic renal cell carcinoma (MRCC), received interferon alpha-2b (IFN-A) 10 x 10(6) units/day IM for 5 days followed by continuous i.v. infusion of interleukin-2 (IL-2) 18 x 10(6) units/day for 5 days. The median follow-up was 10 months. We observed four partial responses (20%), 13 stable (65%) and three progressive diseases (15%). The mean CD4/CD8 ratio, obtained before therapy in patients with MRCC, was compared with CD4/CD8 ratio in 51 patients with different advanced malignancy and in patients with no cancer. The CD4/CD8 ratio was higher in patients with MRCC (2.55) than in other cancers (1.474) and than in populations with no cancer (1.66 x chi 2 = 17,378). The surface phenotypes of peripheral lymphocytes were analysed by cytofluorometry in patients with MRCC during and after treatment with IFN-A and IL-2. Immune modulatory effects of therapy immediately induced a decrease of different sub-populations of lymphocytes except CD25+. Far from the first course, a rise in lymphocyte count was observed. The proliferation effect was as follows: CD4+, CD8+, CD4+ CD45RA- and CD16+ CD8- cells. Far from the second and 3rd course, the sub-populations of lymphocytes decreased, except the CD4+ and CD4- CD45RA+ cells. The CD4/CD8 ratio increased progressively during treatment. Before each course, the CD4/CD8 ratio of patients with response to treatment was higher than the CD4/CD8 ratio of patients with no response. Results were non-significant due to the small number of subjects with responses in this study.
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PMID:[Cancer of the kidney: changes in blood lymphocyte subsets induced by treatment with interferon alpha-2b and interleukin-2r]. 817 84

We report the occurrence of cutaneous sarcoid-like granulomas in one patient with common variable immunodeficiency and another with 'thymoma and hypogammaglobulinaemia'. To our knowledge, this is the first time that such skin lesions have been described in patients with primary immunodeficiency. These granulomas may be attributed to a combination of interleukin-2 deficiency and a profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular eruption' associated with human immunodeficiency virus infection, and might reflect a common pathogenic mechanism.
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PMID:Cutaneous sarcoid-like granulomas in primary immunodeficiency disorders. 830 1

We studied clinical and immunological changes of the post-transfusional syndrome like graft versus host disease (GVDH) in six patients after open heart surgery and in one patient after hepatectomy. In the patient with hepatocellular carcinoma, transcatheter arterial embolization had been previously done. All patients received homologous blood transfusion during and after surgery and erythroderma associated hyperthermia occurred approximately 10 days after operation. Patients receiving open heart surgery died on between postoperative 17th and 21st day. One patient with hepatectomy died on the 29th day after operation. Skin biopsies in all patients showed the findings of acute GVHD. The number of CD3+ and CD4+ T lymphocytes decreased at postoperative day 1, however, the number of CD3+ T lymphocyte increased in three patients after postoperative day 14. The postoperative value of interleukin-2 production was low in patients in whom the value was measured. The immunological status in host has not been clearly resolved. However, the postoperative changes of lymphocytes subsets were abnormal and IL-2 production in two patients showed low level. Therefore, it was considered that pre and postoperative measurement of cell-modiated immunity might predict the occurrence of the post-transfusional GVHD and might be one of useful examinations to prevent the disease.
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PMID:[Post-transfusional syndrome like graft versus host disease]. 839 30

Analysis of the events that regulate development of red blood cells or granulocytes has led to therapies altering clinical conditions associated with anemia or neutropenia. The development of therapeutic approaches to target conditions associated with lymphopenia, such as AIDS, has been thwarted by limited techniques for studying T-lymphocyte development. We describe an in vitro system in which human bone marrow CD34+ cells proliferate, acquire the expression of the lymphoid-specific RAG-2 gene and a broad repertoire of rearranged T-cell receptor genes, develop the ability to produce T cell-specific interleukin-2 and achieve a range of T-cell immunophenotypes. The cells also become susceptible to infection with the T-lymphotropic strain of human immunodeficiency virus-1, HIV-1IIIB. This culture system induces human T lymphopoiesis and may permit further analysis of the events regulating human T-lineage differentiation. It provides a preclinical model for screening stem cell gene therapies directed toward AIDS.
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PMID:Generation of human T lymphocytes from bone marrow CD34+ cells in vitro. 856 38

2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) is an immunosuppressive component of caramel food colouring that causes lymphopenia in mice and rats by an unknown mechanism. In this study we investigated some of the affects of THI on the murine immune system. Initially we showed that splenic T lymphocytes from mice treated with 50 mg/l THI in their drinking water were unable to launch a mixed lymphocyte reaction (MLR) against allogeneic stimulator cells, and had decreased and delayed interleukin-2 (IL-2) production. However, these T cells exhibited a normal proliferative response to concanavalin A (Con A), immobilized anti-CD3 monoclonal antibody (mAb) and anti-CD3 plus anti-CD28 mAb. Furthermore, the MLR response could be restored by the addition of IL-2 to the MLR culture. Homing studies using intravenous injection of fluorescence-labelled splenocytes showed that THI treatment decreased absolute numbers of labelled T and B lymphocytes in the blood and the spleen. Furthermore, these labelled cells reappeared in the blood and the spleen when mice were taken off THI, indicating that lymphocyte recirculation and splenic homing were modified reversibly by THI treatment. Cessation of THI treatment also resulted in a rapid reappearance of MLR responsiveness in the spleen, indicating that THI treatment does not functionally impair recirculating T cells. Collectively these data are compatible with the concept that a rapidly recirculating population of T cells, which produce IL-2 in an allogeneic MLR, are lost from the blood and spleen following THI treatment, and are sequestered in other, yet to be identified, tissues.
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PMID:The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells. 866 39

We assessed the naturally occurring T-cell immune response in primary renal cell carcinoma (RCC) tumors from 12 unselected patients. A predominance of CD3+ T-cell receptor (TCR)alpha/beta+ T cells was observed in tumor-infiltrating lymphocytes (TILs), in contrast with peripheral blood lymphopenia found in some patients. Activation antigen expression on TILs revealed an imbalance in the activation status, with a significant percentage of CD69+ and HLA-DR+ and a low percentage of CD25+ and CD71+ TILs. The lymphocyte activation gene-3 (LAG-3) was detected in some TIL subpopulations and especially in one patient in whom TILs were predominantly TCR alpha/beta+CD8+DR+LAG-3+. In addition, we found that RCC TILs are polarized to a global type 1-like (Th1/Tc1) differentiation pattern (strong secretion of interferon-gamma and interleukin-2 (IL-2) following CD3/TCR crosslinking) but are under the influence of the down-modulatory cytokines IL-6 (secreted by tumor cells) and IL-10, within the tumor microenvironment. In 3 of 5 patients, clonal T-cell expansion at the tumor site was found for several Vbeta specificities, suggesting that in situ stimulation of specific clonotypes in response to potential tumor antigens is a frequent event in RCC. Furthermore, in one patient, selective intratumor amplification of a Vbeta1 subpopulation (5% of TCR alpha/beta+ cells) corresponding to 2 distinct Vbeta1-Jbeta1.6 and Vbeta1-Jbeta2.3 tumor-specific MHC class I-restricted cytotoxic T lymphocytes supports the view that discrete T-cell subsets contribute readily to in situ immunosurveillance.
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PMID:Analysis of T-cell immune response in renal cell carcinoma: polarization to type 1-like differentiation pattern, clonal T-cell expansion and tumor-specific cytotoxicity. 924 86

We have reported a 27% overall anti-tumor response using i.p. immunotherapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re-targeted with bi-specific monoclonal antibody OC/TR, combined with soluble OC/TR and low-dose recombinant interleukin-2 (IL-2). This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4-, 8+, 16-, 56-. Their OC/TR-re-targeted cytolytic activity against Igrov-1 ovarian-carcinoma cells was approximately as high in responders as in non-responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4-, 8+) and they were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov- 1 cells was low in direct assays, and only slightly increased after additional in vitro re-targeting with OC/TR. Systemically, the i.p. immunotherapy resulted in a transient lymphopenia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentrations of free, functional OC/TR, and very weak coating of circulating T lymphocytes with OC/TR. These peripheral-blood T lymphocytes did not exert OC/TR-re-targeted cytolytic activity. Thus, locoregional OC/TR-re-targeted cellular immunotherapy resulted in substantial local immunomodulation and anti-tumor effects but virtually no systemic immunomodulation.
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PMID:Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re-targeted by a bi-specific monoclonal antibody. 933 45

The use of gene targeting techniques has led to new insights into the physiologic function of lymphoid growth factors, their receptors, and associated signal transduction molecules in the formation and function of T and B cells. Mice rendered deficient for the growth factors interleukin-2 or interleukin-4 exhibit impairment in certain immune responses and in steady-state immune function, although production and expansion of lymphocyte populations is unaffected. In contrast, mice deficient for interleukin-7 show a severe lymphopenia in most lymphoid tissues. Interleukin-2, interleukin-4, and interleukin-7 all utilize the common gamma (gamma c) receptor component at the cell surface of lymphocytes and the Jak3 kinase molecule to transduce signals inside the cell. Both gamma c- and Jak3 kinase-deficient animals display a phenotype similar to interleukin-7-deficient animals in terms of lymphoid development. Collectively, these genetic experiments clearly define different in vivo roles for these lymphoid factors. Interleukin-2 and interleukin-4 function by influencing mature lymphocyte populations during immune responses, whereas interleukin-7 plays a singularly dominant role, in terms of the ligands that bind to the gamma c receptor, for the production and expansion of lymphocytes.
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PMID:Physiologic roles of interleukin-2, interleukin-4, and interleukin-7. 937 81


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