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)

We describe the phenotypic characteristics of animals in the fifth backcross-intercross generation of a breeding program in which the RT1 u haplotype and the phenotypic trait responsible for the T-lymphopenia of BB rats have been transferred to the ACI background. In this generation of animals, 24% were lymphopenic with decreased numbers of PBL expressing CD5, TCR alpha, and RT6. The PBL of the lymphopenic animals had a decreased mitogenic response to ConA. All of the nonlymphopenic animals were homozygous for RT6.2. Phenotypic analysis of intestinal IEL revealed that this was also the case for the lymphopenic animals. Moreover, IEL of the lymphopenic animals exhibited a pattern of staining (increased numbers of TCR alpha beta+CD4+CD8+ and decreased numbers of TCR alpha beta+CD4-CD8+) similar to that of BB DP animals. The ACI.1U(BB)-lymphopenic animals, although having two of the genetic traits associated with the expression of spontaneous diabetes mellitus, uniformly fail to develop diabetes. Breeding studies in which these animals were crossed with BB and hBB rats suggest that other genes are necessary for development of overt diabetes.
 ...
PMID:Polygenic nature of spontaneous diabetes in the rat. Permissive MHC haplotype and presence of the lymphopenic trait of the BB rat are not sufficient to produce susceptibility. 144 3

The object of this study was to further characterize the pathophysiology of the peripheral T lymphopenia in the BB rat. Towards this end, surface markers on unseparated thymocytes and purified thymocyte subsets from age- and sex-matched diabetes-resistant (BBn) and diabetes-prone (BBd) rats were analyzed by two-color flow cytometry. The proportions of thymocytes falling into each of the four main phenotypic subsets were comparable in BBn (n = 9) and BBd (n = 8) rats: respectively, 4.6 +/- 0.6% and 4.4 +/- 0.8%, CD4-8-; 68.1 +/- 1.9% and 71.1 +/- 3.2%, CD4+8+; 18.3 +/- 1.5% and 15.4 +/- 2.3%, CD4+8-; 9.1 +/- 0.9% and 9.1 +/- 1.0%, CD4-8+. In addition, absolute numbers of thymocytes were not significantly different. The levels of expression of CD4, TCR-alpha beta within each thymocyte subset were comparable in BBn and BBd animals as were the anti-TCR-induced proliferative responses of their CD4+8- and CD4-8+ thymocytes. However, phenotypic abnormalities within the CD4-8+ thymocyte subset of the BBd rat were found. A very significant (p less than 0.005) deletion of mature CD4-8+, TCR-alpha beta + thymocytes and a proportional increase (p less than 0.005) of immature CD4-8+, TCR-alpha beta low thymocytes. Moreover, a twofold decrease of CD8 expression by mature CD4-8+ thymocytes was observed in BBd animals. These results suggest that an impaired thymic maturation contributes to the peripheral T lymphopenia of the BBd rat.
 ...
PMID:Abnormal thymocyte maturation in spontaneously diabetic BB rats involves the deletion of CD4-8+ cells. 168 92

Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers of autoantibodies to HLA molecules and other surface markers of CD4+ T cells appear to increase with the progression of disease and may correlate with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the immune system. Genesis of autoreactivity may be related to structural homologies of HIV-1 env-products to such functional molecules involved in the control of self-tolerance. The most impressive similarities include the HLA-DR4 and DR2, the variable regions of TCR alpha-, beta-, and gamma-chain, the Fas protein, and several functional domains of IgG and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response, through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could also include the activation of membrane-to-nucleus signal transducers resulting in increased apoptosis. The evolution of autoimmune mechanisms during HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since aspects of oligoclonal immune response to HIV-1 components may occur in several autoimmune diseases which in some instances evolve to lymphoma.
 ...
PMID:Autoreactivity in HIV-1 infection: the role of molecular mimicry. 776 37

Converging data suggest an important role for IL-7 in T lymphocyte maturation as illustrated by the severe T lymphopenia observed in IL-7-deficient mice. We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. These T cells, designated as NK1+ T cells, have the unique property among thymocytes of producing large amounts of IL-4 upon primary stimulation via the TCR. We have further demonstrated that thymic NK1+ T cells of non-obese diabetic (NOD) mice, a spontaneous model of autoimmune type I diabetes, are markedly deficient in maturation both quantitatively and functionally (IL-4 production). In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. Importantly, this activity of IL-7 on NK1+ T cells was also demonstrated in non-autoimmune strains of mice. These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. These findings confirm the role of IL-7 in NK1+ T cell maturation and suggest that the NK1+ T cell defect in NOD mice could be related to insufficient intrathymic IL-7 bioavailability.
 ...
PMID:IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse. 894 70

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.
 ...
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

T cell fate following antigen encounter is determined by several intracellular signals generated by the interaction of the T cell with an antigen-presenting cell. In the periphery activation requires T cell receptor signaling (signal one) in combination with costimulatory signals (signal two), usually provided through the cognate interaction of CD28 and B7 molecules. Provision of signal one alone to purified murine peripheral T cells in vitro induces apoptosis or anergy rather than promoting activation. These T cells can be rescued from apoptosis if they are provided with costimulation supplied, for example, by engaging the CD28 co-receptor with an anti-CD28 monoclonal antibody or by adding an exogenous source of interleukin-2. However, a majority of peripheral T cells from autoimmune, diabetes-prone Biobreeding (BB) rats exhibited different responses to these stimuli. T cells from these rats could not be rescued from apoptosis by costimulation. This was not due to the inability of BB-DP T cells to upregulate CD28 and the IL-2 receptor in response to TCR crosslinking. The failure of these costimulatory interactions to rescue BB-DP T cells segregated with the diabetes-susceptibility gene iddm1. Iddm1 in the rat causes peripheral T cell lymphopenia, which is associated with a dramatically shortened peripheral T cell life span. Our results indicate that a diabetogenic gene may contribute to autoimmunity by negating costimulatory signals important for the survival of long-lived peripheral T cells.
 ...
PMID:A diabetogenic gene prevents T cells from receiving costimulatory signals. 1035 84

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

CVID is a primary immune disorder in which hypogammaglobulinaemia may be associated with a number of T cell defects including lymphopenia, anergy, impaired lymphocyte proliferation and deficient cytokine secretion. In this study we show that T cells of CVID subjects, in comparison with control T cells, undergo spontaneous apoptosis in culture and markedly accelerated apoptosis after gamma-irradiation. Although costimulation of the CD28 receptor following engagement of the TCR/CD3 receptor normally provides a second signal necessary for IL-2 secretion, CD28 costimulation in CVID does not significantly increase IL-2 production, nor does this combination of activators enhance the survival of irradiated CVID T cells, as it does for cultured normal T cells. Addition of IL-2 enhances CVID T cell survival, suggesting that the IL-2 signalling pathways are normal. CVID T cells have similar expression of Bcl-2 to control T cells. CD3 stimulation up-regulates T cell expression of bcl-xL mRNA for normal T cells, but anti-CD28 does not augment bcl-xL expression for CVID subjects with accelerated apoptosis. Defects of the CD28 receptor pathway, leading to cytokine deprivation and dysregulation of bcl-xL, could lead to poor T cell viability and some of the cellular defects observed in CVID.
 ...
PMID:Enhanced apoptosis of T cells in common variable immunodeficiency (CVID): role of defective CD28 co-stimulation. 1084 30

We previously demonstrated that the rat thymus undergoes a progressive remodelling long before the appearance of typical signs of involution [Quaglino, D., Capri, M., Bergamini, G., Euclidi, E., Zecca, L., Franceschi, C., Pasquali Ronchetti, I., 1998. Age-dependent remodelling of rat thymus. Morphological and cytofluorimetric analysis from birth up to one year of age. Eur. J. Cell. Biol. 76, 156-166]. To focus better on the complex remodelling that occurs in the rat immune system during the first year of life, we analysed the phenotype profile of thymocytes, and T lymphocytes from mesenteric lymph nodes and peripheral blood of the same animals by flow cytometry. Two experimental sets were performed simultaneously using the same animal strain, but starting and ending the study at different ages (15 days up to 300 days in the first experimental set, and 90 days up to 360 days of life in the second). In the rat these ages appear to be crucial not only for developmental, maturative and early involutional processes of the thymus, but also of the entire immune system. The main findings were the following: (1) in the thymus, CD8(-)CD4(-) cells increased, CD5(+)alphabeta TCR(-) and CD8(+)CD4(+) thymocytes decreased, while the most mature cell subset appeared well preserved with ageing; (2) in the lymph nodes, T helper and T cytotoxic lymphocytes decreased in the most aged animals. Memory/activated CD4(+)CD45RC(-) T cells decreased, while naive/resting CD4(+)CD45RC(+) cells increased in the youngest animals and decreased in the oldest. CD8(+)CD45RC(-) and CD8(+)CD45RC(+) lymphocytes showed a complex age-dependent trend, and (3) in peripheral blood, minor modifications were evident, such as an age-dependent increase in the alphabeta TCR(+)CD25(+) cell subset. Some of these changes were related to the developmental process, while others could likely be interpreted as early signs of immunosenescence. The role of these modifications in immune system is discussed within the framework of the remodelling hypothesis of immunosenescence. The age-dependent changes in these three lymphoid compartments, however, appear to be different and only partially overlapping, thus suggesting that the maturational, developmental and ageing processes have distinct characteristics in the central and peripheral lymphoid organs.
 ...
PMID:A cytofluorimetric study of T lymphocyte subsets in rat lymphoid tissues (thymus, lymph nodes) and peripheral blood: a continuous remodelling during the first year of life. 1097 83

Leukopenia, in particular lymphopenia, is a characteristic early event during classical swine fever (CSF). This was the case in both highly virulent (CSF virus (CSFV) strain Brescia) and moderately virulent (CSFV Uelzen) infections. The leukopenia involved leukocyte sub-populations in a disparate manner, with B-lymphocytes, helper T-cells and cytotoxic T-cells being the most affected. Depletion of lymphocyte sub-populations occurred 1-4 days before virus could be detected by RT-PCR in the serum. With the virulent Brescia virus, depletion was evident by 2 days post-infection (p.i.) but not until 3 days p.i. with an equivalent dose of the low virulent Uelzen strain. A lower (1000-fold) dose of the latter virus delayed these kinetics. gammadelta-TCR(+) T-cells were also reduced, but more so with the virulent Brescia infection. The final level of B-and alphabeta-T-cell lymphopenia was similar for all animals, including those infected with the lower virus dose. AnnexinV staining revealed that cell viability was clearly diminished, particularly interesting, considering the clinical differences between infections by Brescia and Uelzen viruses. It was the time p.i. and rate of appearance of dying cells which was more rapid in the virulent Brescia infections. Interestingly, the repeated blood sampling resulted in depletion of some leukocyte populations also in non-infected control animals. Particularly neutrophils and NK cells, and to a lower extent CD4(+), CD8(+) T-lymphocytes and B-lymphocytes were affected. Taken together, the data show that the alphabeta-T-lymphocyte subsets are particularly susceptible to modulation during the acute phase of CSF, being detectable before the onset of viraemia. The pathogenic mechanism therein would involve indirect virus-host interactions, probably originating from the site of primary infection, rather than a direct effect of the virus or viral protein. Furthermore, these characteristics offer an explanation for the retardation of the cellular and humoral immune response observed during classical swine fever.
 ...
PMID:Depletion of CD4(+) and CD8(high+) T-cells before the onset of viraemia during classical swine fever. 1118 44


1 2 3 4 5 6 7 8 9 10 Next >>