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

Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD-support as a bridge to heart transplantation. This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD-support. Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart). We did not find significant differences in preoperative values of immune parameters between groups of survivors (n = 14) and non-survivors (n = 16). All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T-cell activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T-lymphopenia. Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion. These observations point to the reduced antimicrobial immunity ("immunoparalysis") in the non-survivors and may explain the fatal course of infection in these individuals. The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD-patients.
 ...
PMID:Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation. 813 71

Circulating lymphocyte subset imbalance is associated with type-1 insulin-dependent diabetes mellitus (IDDM). To examine the imbalance in these immunoregulatory cells in Kuwaitis with type-1 diabetes and their first-degree relatives we analysed T-lymphocyte subsets and HLA-DR expression (activation) in 18 IDDM patients with a family history of IDDM and 18 non-diabetic first-degree relatives of the IDDM patients. Both IDDM patients and their first-degree relatives showed a mild lymphopenia. Total T lymphocytes, CD3+ cells, in IDDM patients and their first-degree relatives were reduced compared to control subjects (P < 0.001). Total B lymphocytes, CD19+ cells, was increased in IDDM patients (P = 0.001), but was comparable to controls in IDDM patients' first-degree relatives. No quantitative abnormality was demonstrated in CD4+ cells in IDDM patients; however, these cells were higher in their first-degree relatives (P = 0.0089). Suppressor T lymphocytes, CD8+ cells, in first-degree relatives and controls were not significantly different; however, these cells were significantly reduced in IDDM patients (P = 0.001). The ratio of CD4+/CD8+ cells was higher in IDDM patients and their first-degree relatives compared to controls (P = 0.0007 and 0.0103, respectively). Activated T lymphocytes, HLA-DR+ CD3+ cells, were significantly increased in IDDM patients and their first-degree relatives. HLA-DR3 was the most common antigen found in IDDM patients (77% vs. 20% in controls, P = 0.00021). The second most common antigen was HLA-DR4 (55% vs. 24% in controls, P = 0.0566). However, no relationship was found in the levels of CD3+, CD4+ or CD8+ cells in patients possessing either DR3 or DR4. These results suggest that T-lymphocyte subset imbalance not only characterizes the cellular autoimmunity in the pathogenesis of IDDM but may also be significant in early pre-diabetic stages in those with a family history of IDDM.
 ...
PMID:Abnormal lymphocyte subsets in Kuwaiti patients with type-1 insulin-dependent diabetes mellitus and their first-degree relatives. 874 21

The clinical manifestations of AIDS are predominantly due to the cellular and humoral immune dysfunction caused by HIV infection, and thymic dysplasia caused by HIV infection probably contributes to the T cell lymphopenia. In the present study, T cell differentiation and/or maturation was assessed when enriched CD34+ stem cells (SCs or SC) purified from bone marrow of HIV-seropositive hemophiliacs were cocultured with allogeneic cultured thymic epithelial fragments (CTEFs). When HIV-seropositive hemophiliacs' enriched CD34+ SC were cocultured with allogeneic CTEFs, acquisition of the T cell phenotypic markers CD7, CD2, CD3, CD4, CD8 and T cell receptor for antigen (TCR) alpha beta was observed from cells harvested from the culture media peaking at approximately 28 days. Origin of the differentiated and matured T cells from the CD34+ SC was confirmed by labeling the SC with 5-(and -6)-(((4-chloromethyl)benzoyl)amino)tetra-methyl-rhodamine (CMTMR), a fluorescent cytoplasmic dye, and detecting fluorescence in the differentiated and matured T cell by flow cytometry. In one experiment, CMTMR labeling was omitted and double positive CD4+CD8+ and triple positive CD3+CD4+CD8+ thymocytes were identified. These studies confirmed that thymocyte differentiation/maturation from SC had occurred. In addition, T cells obtained from the CD34+ SC and CTEF cocultures proliferated to phytohemagglutinin stimulation maximally with stem cell donor antigen-presenting cells (APCs) and also proliferated to pooled B cells in a mixed lymphocyte culture (MLC). Furthermore, the T cells produced were tolerant to thymus donor B cell HLA antigens (p < 0.025); though there was slight MLC reactivity to autologous stem cell donor B cell HLA compared to thymic B cells (p < 0.025). These T cells demonstrated positive self-alloreactivity to stem cell HLA antigens in four of nine persons, though decreased compared to pool B cell alloantigens. Furthermore, in three experiments, responsiveness to stem cell donor B cells subsequently disappeared upon further duration of CD34+ SC-CTEF coculture. These studies suggested that CD34+ SC gave rise to accessory cells populating the thymus that contributed to HLA restriction. To further evaluate this hypothesis, two different donors of CD34+ SC were cultured simultaneously with thymic epithelial fragments and MLC reactivity was then examined toward APC of the stem cell donors. In these experiments, T cells responded to stimulation with HLA antigens of the pool B cells and did not respond to thymus donor B cells. In six of eight experiments, the chimeric SC-CTEF T cells did not respond to stimulation with B cells of either stem cell donor. These studies suggest that HLA restriction and tolerance were induced by cells of the stem cell donor as well as the thymic epithelial cell HLA antigens. In summary, these studies demonstrated that HIV-infected hemophiliac bone marrow-derived nonadherent CD34+ SC were capable of differentiating and/or maturing into T cells when cocultured in a normal allogeneic thymic environment. Furthermore, the T cells derived from derived CD34+ SC were capable of differentiating into T cells when cocultured in a normal allogeneic thymic environment, proliferated maximally with APCs from the stem cell donor and were tolerant of thymic HLA class II antigens, and to a lesser degree to stem cell donor B cell HLA antigens.
 ...
PMID:T cell differentiation/maturation of CD34+ stem cells from HIV-seropositive hemophiliacs in cultured thymic epithelial fragments. 882 Sep 59

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.
 ...
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

A subgroup of common variable immunodeficiency (CVID) patients have distinct clinical features, particularly granulomata splenomegaly, characteristic blood lymphocyte phenotype, and elevated circulating TNF levels. To investigate the genetic basis for this phenotype, 150 CVID patients and 200 controls were genotyped for six biallelic TNF and lymphotoxin-alpha (LT alpha) polymorphisms and eight class I and II HLA loci using PCR and sequence specific primers (PCR-SSP) sequence-specific primers. Clinical and immunophenotypic data were collected for 90 patients to examine associations with CVID patient subgroups. The presence of granulomata (22% of patients) was strongly associated with splenomegaly, T and B lymphopenia, reduced CD4+ CD45RA+ T cells, and CD8+ CD57+ lymphocytosis, confirming the concept of a subgroup of patients with distinct clinical and laboratory features. The uncommon TNF +488A allele was strongly associated with this subgroup (p = 0.0005). The association between "granulomatous" CVID and TNF +488A was independent of HLA class I and II associations. We postulate that the presence of the TNF +488A allele, or alleles in linkage disequilibrium with it, contributes to the high levels of TNF and granulomatous complications characteristic of this subgroup of patients.
 ...
PMID:TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. 955 Apr 27

The efficacy of primary prophylactic treatment for opportunistic infections can be estimated in an observational cohort study by adjusting for clinical and laboratory markers of the immunodeficiency (e.g., oral candidiasis, CD4%, lymphocyte cell counts) as time-dependent co-variates (providing that the treatment does not directly alter the markers). However, the CD4 cell count provides an incomplete measure of the protective immune response, and the efficacy of treatment may be underestimated if there is inadequate adjustment for the severity of immunodeficiency. Unlike prophylactic therapies, the efficacy of which remains relatively constant over time, antiretroviral therapy may produce only transient or time-limited benefits. This problem can be minimized by allowing the effect of antiretroviral therapy to vary over time in Cox proportional hazards models (i.e., to allow the antiretroviral therapy coefficient to change over time). Another difficulty is that CD4 cell counts may underestimate the degree of immunodeficiency after prolonged zidovudine (AZT) monotherapy. If post-antiretroviral therapy CD4 cell counts are used to adjust for the stage of immunodeficiency, it may therefore be helpful to adjust for the duration of antiretroviral therapy with the CD4 cell count at the time of starting antiretroviral therapy. It is interesting to consider statistical models of progressive HIV-induced immunodeficiency in the context of the evolution of host immunity. HIV infection results in the loss of the relatively recently evolved adaptive CD4 T cell-mediated immunity to intracellular parasites. The infected host may compensate for this by making greater use of phylogenetically ancient, more innate protective responses. Because these compensatory responses are polymorphic, this results in the appearance of differences between individuals in the immune response to HIV as the disease progresses. Data from the Western Australia HIV Cohort Study support a two-stage model of immunopathology. The first stage of this model involves a loss of mucosal immunity and occurs at a variable CD4 cell count (of between 400 cells/mm3 and zero), and is marked by a loss of cutaneous delayed-type hypersensitivity responses and oral candidiasis, seborrheic dermatitis, and Pneumocystis carinii pneumonia. The second stage of the model involves a loss of systemic immunity and requires profound CD4 T-cell lymphopenia (CD4 cell count <50 cells/mm3), and is marked by infections such as cytomegalovirus and disseminated Mycobacterium avium infection. The influence of HLA type on the risk for such opportunistic infections becomes apparent during this late phase.
 ...
PMID:The Western Australian HIV Cohort Study, Perth, Australia. 958 48

Bronchial inflammation plays a central role in asthma. We investigated whether parameters of inflammation were increased in peripheral blood. Furthermore, we tested whether fluticasone propionate (FP), a new inhaled corticosteroid (ICS), and beclomethasone dipropionate (BDP) affected these parameters. FP 750 microg/day and BDP 1500 microg/day were compared in a randomized, crossover study consisting of two 6-week treatment periods, each preceded by a 3-week placebo period. Twenty-one patients with symptomatic asthma completed the study. The results were compared with those of six normal subjects (controls). Immunophenotyping of inflammatory cells was performed in whole blood, and serum eosinophil cationic protein (ECP) was measured. With regard to clinical efficacy, ICS increased PC20 histamine by more than 1.9 doubling doses and FEV1 by more than 0.34 l. The number of CD3/HLA-DR+ lymphocytes was significantly increased in asthmatics compared to the normal subjects, both after placebo (P<0.01) and after therapy (P<0.05). The CD3/HLA-DR+ lymphocytes decreased significantly after treatment with FP (P<0.05). Serum ECP was elevated in patients without ICS and decreased after treatment with BDP (P<0.001). In conclusion, the number of CD3/HLA-DR+ lymphocytes and serum ECP levels were raised in the peripheral blood of symptomatic asthmatics, and decreased by clinically effective doses of ICS. In this respect, FP 750 microg/day was at least as effective as BDP 1500 microg/day.
 ...
PMID:Effects of fluticasone propionate and beclomethasone dipropionate on parameters of inflammation in peripheral blood of patients with asthma. 970 34

Infection with atypical mycobacteria occurs mainly in patients with a compromised cellular immune system, in particular in those with a defective T cell or monocyte function. Here we analyzed the specific immune response of an adolescent HIV-negative patient with disseminated mycobacterium avium infection and fatal varizella zoster virus infection. The patient presented with dysplastic hematopoesis of all cell lineage's and a bicytopenia of erythrocytes and leukocytes, but a hematological malignancy could not be found. We found a peripheral lymphopenia and monocytopenia, as well as a lack of NK-cells and B-cells. Lymphocytes consisted of 95% T cells, which contained up to 40% of TCR gammadelta+CD4-CD8-T-cells (mainly TCR gamma9delta2), few monocytes and B-cells. Approximately 50% of CD3+ T-cells showed a CD57+ NK-like phenotype. Functional analysis of PBMC revealed a good antigen-specific T cell function if antigen-presenting cells were supplemented from a HLA-matched donor. Moreover, a strong M. avium specific cytotoxicity mediated by TCR alphabeta+T-cells could be found in vitro and even ex vivo. In contrast, NK-killing was absent. No evidence for a defect in IL-12 or IFN-gamma production and signaling were found. The data indicate that a strong alphabeta and gammadelta T cell immunity tries to compensate for a deficient monocyte and NK cell function in this patient.
 ...
PMID:Strong alpha beta and gamma delta TCR response in a patient with disseminated Mycobacterium avium infection and lack of NK cells and monocytopenia. 1084 41

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)
 ...
PMID:Increased apoptosis of peripheral blood T cells following allogeneic hematopoietic cell transplantation. 1084 17

We report a case of a combined immunodeficiency (CID) in a child affected by trichothiodystrophy (TTD) characterized by an altered response to ultraviolet (UV) light due to a defect in the XPD gene. The XPD gene encodes a subunit of the transcription factor II H (TFIIH), a complex involved in nucleotide-excision repair (NER) and basal transcription. Our patient showed neurological and immune system abnormalities, including CD4 + lymphopenia never previously reported in TTD patients. In vitro immunological studies revealed a marked reduction in T-cell proliferation in response to mitogens and CD3 cross-linking which was partially recovered by the addition of anti-CD28 antibody or exogenous interleukin-2. The patient's T cells displayed alterations in T-cell receptor (TCR/CD3) proximal signalling characterized by marked reduction in Lck kinase activity coupled with a constitutive hyperactivation of Fyn kinase. Despite these alterations, normal levels of Lck and Fyn proteins were detected. The role of antigen-presenting cells (APCs) in the pathogenesis of the T-cell defect was investigated by analysing dendritic cells (DCs) generated from the patient's blood monocytes. In these cells, flow cytometry revealed significantly reduced expression of the CD86 co-stimulatory molecules and HLA glycoproteins. In addition, the patient's DCs showed a decreased ability to stimulate naive T lymphocytes. Overall, the results of our study suggest that a defective TFIIH complex might result in alterations in T cells and DC functions leading to a severe immunodeficiency.
 ...
PMID:Defective dendritic cell maturation in a child with nucleotide excision repair deficiency and CD4 lymphopenia. 1173 70


<< Previous 1 2 3 4 5 6 Next >>