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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.
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PMID:Basic and clinical immunology. 1261 48

As well as the proliferation of antigen-specific T and B cells the programmed cell death (apoptosis) of lymphocytes is one of the key mechanisms of the immune homeostasis regulation. The apoptosis of immunocytes is associated with the expression of Fas/Apo-1 (CD95) glycoprotein. The expression of Fas/Apo-1 (CD95) on the peripheral blood lymphocytes from 45 healthy donors and 45 patients with pulmonary tuberculosis was studied. The percentage of CD95(+) lymphocytes of the healthy donors was 40.1 +/- 10.9, significant correlation of this parameter with the percentage of CD3(+) and CD4(+) lymphocytes was observed. In patients with pulmonary tuberculosis the percentage of CD95(+) lymphocytes was 47.0 +/- 15.9. In this case the correlations between the percentage of CD95(+) lymphocytes, CD72(+) B cells, CD25(+) lymphocytes and HLA DR(+) cells and serum IgA level were observed. Using the procedure of cluster analysis it was shown that extremal number of the CD95(+) lymphocytes is typical for the patients with the prognostically unfavorable immune abnormalities and clinic picture, high levels of serum TNFalpha and hypercortisolemia. It is tempting to speculate that apoptosis of T cells (possibly Th1 cells) is of great importance in the pathogenesis of the immunodeficiency associated with the micobacteriosis.
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PMID:Fas/Apo-1 (CD95) Antigen Expression on the Peripheral Blood Lymphocytes in Healthy Donors and Pulmonary Tuberculosis Patients. 1268 14

The immune status and the PBL apoptosis were studied in the healthy donors and the opioid addicts. Leukocytosis and the increased percentage of the CD3(+) T cells, CD8(+) T cells, CD19(+) B cells, activated CD25(+) and HLA DR(+) lymphocytes were observed in the addicted patients. The number of the CD95 and CD95L bearing cells also was increased however the percentage of the bcl-2(+) lymphocytes was the same as for the donors. The activated PBL subset "pattern" was accompanied by increased IgM level, decreased IgG and IgA levels and elevated serum IL-1beta and TNFalpha. PBL mitogenic response and LPS-induced IL-1beta, TNFalpha and IFNalpha production were suppressed in the opioid addicts. These changes were associated with the increased level of the spontaneous PBL apoptosis, which was documented by morphological method and caspase 3 activity evaluation. The anti-CD3mAbs-induced T-cell apoptosis in the 72-h cultures also was increased however the activated T cells from the addicted patients were resistant to the dexamethasone-induced apoptosis. The immune abnormalities were more prominent in patients with the clinically manifested infectious immunopathological syndrome. Thus, the activation-induced lymphocyte apoptosis may be the factor of importance in the mechanisms of the immunodeficiency in the opioid addicts.
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PMID:The Immune Status and Lymphocyte Apoptosis in the Opioid Addicts. 1268 28

Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi's sarcoma (KS), encodes a chemokine receptor homologue, the viral G protein-coupled receptor (vGPCR), that has been implicated in KS pathogenesis. Expression of vGPCR constitutively activates several signaling pathways, including NF-kappa B, and induces the expression of proinflammatory and angiogenic factors, consistent with the inflammatory hyperproliferative nature of KS lesions. Here we show that vGPCR also constitutively activates the nuclear factor of activated T cells (NF-AT), another transcription factor important in regulation of the expression of inflammatory cytokines and related factors. NF-AT activation by vGPCR depended upon signaling through the phosphatidylinositol 3-kinase-Akt-glycogen synthetase kinase 3 (PI3-K/Akt/GSK-3) pathway and resulted in increased expression of NF-AT-dependent cell surface molecules (CD25, CD29, Fas ligand), proinflammatory cytokines (interleukin-2 [IL-2], IL-4), and proangiogenic factors (granulocyte-macrophage colony-stimulating factor GMCSF and TNF alpha). vGPCR expression also increased endothelial cell-T-cell adhesion. Although infection with HHV-8 is necessary to cause KS, coinfection with human immunodeficiency virus type 1 (HIV-1), in the absence of antiretroviral suppressive therapy, increases the risk of KS by many orders of magnitude. NF-AT and NF-kappa B activation by vGPCR was greatly increased by the HIV-1 Tat protein, although Tat alone had little effect on NF-AT. The enhancement of NF-AT by Tat appears to be mediated through collaborative stimulation of the PI3-K/Akt/GSK-3 pathway by vGPCR and Tat. Our data further support the idea that vGPCR contributes to the pathogenesis of KS by a paracrine mechanism and, in addition, provide the first evidence of collaboration between an HIV-1 protein and an HHV-8 protein.
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PMID:Human herpesvirus 8-encoded vGPCR activates nuclear factor of activated T cells and collaborates with human immunodeficiency virus type 1 Tat. 1271 69

Deficiency of SAP (SLAM (signaling lymphocyte activation molecule)-associated protein) protein is associated with a severe immunodeficiency, the X-linked lymphoproliferative disease (XLP) characterized by an inappropriate immune reaction against Epstein-Barr virus infection often resulting in a fatal clinical course. Several studies demonstrated altered NK and T cell function in XLP patients; however, the mechanisms underlying XLP disease are still largely unknown. Here, we show that non-transformed T cell lines obtained from XLP patients were defective in several activation events such as IL-2 production, CD25 expression, and homotypic cell aggregation when cells were stimulated via T cell antigen receptor (TCR).CD3 but not when early TCR-dependent events were bypassed by stimulation with phorbol 12-myristate 13-acetate/ionomycin. Analysis of proximal T cell signaling revealed imbalanced TCR.CD3-induced signaling in SAP-deficient T cells. Although phospholipase C gamma 1 phosphorylation and calcium response were both enhanced in T cells from XLP patients, phosphorylation of VAV and downstream signal transduction events such as mitogen-activated protein kinase phosphorylation and IL-2 production were diminished. Importantly, reconstitution of SAP expression by retroviral-mediated gene transfer completely restored abnormal signaling events in T cell lines derived from XLP patients. In conclusion, SAP mutation or deletion in XLP patients causes profound defects in T cell activation, resulting in immune deficiency. Moreover, these data provide evidence that SAP functions as an essential integrator in early TCR signal transduction.
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PMID:SLAM-associated protein deficiency causes imbalanced early signal transduction and blocks downstream activation in T cells from X-linked lymphoproliferative disease patients. 1276 68

Intermittent administration of interleukin (IL)-2 produces significant and sustained increases in CD4(+) T lymphocyte count in human immunodeficiency virus (HIV)-infected subjects but can be associated with dose-limiting toxicities. The primary objective of this study was to determine whether concomitant administration of prednisone could decrease these toxicities. HIV-seropositive adults receiving highly active antiretroviral therapy (HAART) were randomized to receive either (1) intermittent subcutaneous IL-2 and placebo, (2) intermittent subcutaneous IL-2 and prednisone, (3) intermittent prednisone, or (4) intermittent placebo. Prednisone decreased levels of proinflammatory cytokines during IL-2 cycles but, despite induction of expression of CD25, blunted increases in IL-2-associated CD4(+) T lymphocyte count. Whereas intermittent administration of IL-2 reduced basal proliferation of CD4(+) T cells, this effect was inhibited by prednisone, suggesting that prednisone potentially interferes with IL-2's long-term effects on survival of T lymphocytes.
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PMID:A randomized, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus. 1289 39

Imaging of adoptively transferred cells in vivo by magnetic resonance imaging (MRI) could provide important information on disease-related patterns of lymphocyte homing in nonhuman primate models of AIDS. As a preliminary study to assess the feasibility of visualizing activated rhesus T cells by MRI, anti-CD3/CD28-expanded CD4+ T lymphocytes were labeled in vitro with monocrystalline iron oxide nanoparticles (MION). Intracellular incorporation of MION was determined by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrography (ICP-MS). Pretreatment with colchicine did not affect MION labeling, suggesting that cellular uptake of MION occurred by adsorptive pinocytosis or receptor-mediated endocytosis. TEM analysis revealed that MION were intracellularly compartmentalized exclusively in the cytoplasm and did not cause any measurable physiologic effects on T-cell function, including viability, proliferation, synthesis of select cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma), activation antigens (CD25 and CD69), adhesion molecules (alpha4beta7 and CD49d), and susceptibility to in vitro infection with simian immunodeficiency virus mac239. A sensitivity of 0.05% (1 MION-labeled T cell in 2000 unlabeled cells) could be achieved using T2-weighted gradient echo imaging. Furthermore, under these experimental conditions, the MRI signal did not decrease in proliferating MION-labeled CD4+ T cells over a period of 120 hours. These results indicate that intracellular labeling with MION can be a useful technique for noninvasively monitoring trafficking patterns of adoptively transferred leukocyte subsets in real-time by MRI in nonhuman primate models of AIDS.
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PMID:Magnetic resonance imaging of activated proliferating rhesus macaque T cells labeled with superparamagnetic monocrystalline iron oxide nanoparticles. 1470 87

Regulatory T (T(R)) cells maintain tolerance to self-antigens and control immune responses to alloantigens after organ transplantation. Here, we show that CD4(+) CD25(+) human T(R) cells suppress virus-specific T-cell responses. Depletion of T(R) cells from peripheral blood mononuclear cells enhances T-cell responses to cytomegalovirus and human immunodeficiency virus antigens. We propose that chronic viral infections lead to induction of suppressive T(R) cells that inhibit the antiviral immune response.
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PMID:Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens. 1496 40

Posttransplant lymphoproliferative disorders (PTLD) are a frequent complication in bowel transplant recipients. Histological changes in PTLD range from expansile lymphoplasmacytic (LP) hyperplasia to frank lymphoma. Small bowel allograft biopsies obtained in the first 250 days posttransplant were retrospectively graded after patients had received induction immunosuppression with either anti-CD52 (Campath) or anti-CD25 (Zenapax) monoclonal antibodies. The biopsies were analyzed with respect to the onset intensity of lymphoplasmacytic infiltrates and presence of in situ EBV hybridization (EBER) positivity. We observed that lymphoplasmacytic infiltrates were a frequent change in all bowel transplant patients over the examined period. Campath-treated patients developed earlier LP infiltrates of mild to moderate intensity between day 1 and 100 posttransplant, thereafter decreasing to mild. No EBER positivity was detected in this group. Zenapax-treated patients presented with LP infiltrates later of mild to moderate intensity through day 100 posttransplant. However, more persistent and intense LP infiltrates was observed after day 101 in this group, including a case of lymphoma and two cases of EBER positivity. We conclude that Campath immunosuppression results in an earlier appearance of LP lesions that are generally less intense than those evident with Zenapax. We attribute these findings to the more profound immunodeficiency and cell targeting following Campath treatment.
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PMID:Lymphoplasmacytic hyperplasia (possibly pre-PTLD) has varied expression and appearance in intestinal transplant recipients receiving Campath immunosuppression. 1505 Jan 68

Studies attempting to identify reservoirs of HIV-1 latency have documented that the virus persists as both a latent and productive infection in subsets of CD4(+) cells. Reports regarding establishment of a stable HIV-1 infection in quiescent T cells in vitro, however, are controversial. In the present study, we investigated the susceptibility of naive and activated CD4(+) cell subsets (distinguished by differential expression of CD25) to feline immunodeficiency virus (FIV) infection, their ability to replicate the virus, and potentially act as a reservoir for virus persistence in infected animals. While both CD4(+)CD25(+) and CD4(+)CD25(-) cells are susceptible to FIV infection in vitro and in vivo, only CD4(+)CD25(+) cells produce infectious virions when cultured with interleukin-2 (IL-2). Latently infected CD4(+)CD25(-) cells produce infectious virions following ConcanvalinA (ConA) stimulation, which correlates with upregulated surface expression of CD25. In contrast to CD4(+)CD25(-) cells, CD4(+)CD25(+) cells remain unresponsive to mitogen stimulation and are relatively resistant to apoptosis whether or not infected with FIV. The ability of CD4(+)CD25(+) cells to replicate FIV efficiently in the presence of IL-2 but remain anergic and unresponsive to apoptotic signaling suggests that these cells may provide a reservoir of productive FIV infection. On the contrary, CD4(+)CD25(-) cells seem to establish as latent viral reservoirs capable of being reactivated after stimulation.
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PMID:Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation. 1505 90


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