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

Two immature T cell lines (FT1 and FT4) were established after in vitro cloning of peripheral blood lymphocytes (PBLs) from an asymptomatic human immunodeficiency virus type 1 (HIV-1) seropositive, human T cell-lymphotropic virus type 1 seronegative homosexual subject. Although derived from a limiting dilution cell cloning assay, these cell lines were not recloned for this study. Their growth was independent of exogenous interleukin-2. Both cell lines were able to form colonies when cloned in agar, but failed to form solid tumours when injected into nude mice. FT lines belong to the very immature T cell lineage as they exhibit rearranged TCR genes but no expression of T cell membrane antigens, including CD2, CD3, CD4, CD6, CD7 and CD8. They also contain an HIV-1 genome that was detected only in an extra-chromosomal DNA form, even after several passages in vitro. The presence of unintegrated viral DNA was also detected by polymerase chain reaction analysis in the same sample of fresh uncultured PBLs. Furthermore, despite the absence of CD4 expression, both T cell lines were susceptible to CD4-independent HIV-1 superinfection (lack of superinfection inhibition in the presence of OKT4A monoclonal antibodies).
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PMID:Extrachromosomal human immunodeficiency virus type 1 DNA forms in fresh peripheral blood lymphocytes and in two interleukin-2-independent T cell lines derived from peripheral blood lymphocytes of an asymptomatic seropositive subject. 133 22

We found that naive (CD45RA+) CD4 T cells have a lower capacity of adhesion to Epstein-Barr virus (EBV) immortalized B cells than memory (CD45RO+) CD4 T cells, as judged by conjugate formation. This would appear to be due to differences in the expression of adhesion molecules [lymphocyte function-associated antigen (LFA)-1, CD2]. However, kinetic studies showed that the degree of adhesion of naive T cells to B cells was stable over 60 min while that of memory T cells, like that of unseparated CD4 T cells, was characterized by a rapid formation and rapid dissociation of conjugates. This could be explained by a difference in the sensitivity of naive and memory CD4 T cells to down-regulation of antigen-independent adhesion by CD4-MHC class II interaction. Indeed, memory T cells also adhered stably to MHC class II(-) B cells. The adhesion of memory T cells, but not naive T cells, to MHC class II(+) B cells was sensitive to inhibition by OKT4a an anti-CD4 antibody, human immunodeficiency (HIV) gp160 (env) protein and a 12-mer peptide encompassing the 35-46 sequence of the HLA, DR beta 1 domain and previously shown to inhibit activation of HLA class II-restricted CD4 T cell responses. Since MHC class II expression did not influence the degree of conjugate formation by naive or memory CD4 T cells with B cells, CD4-MHC class II interaction does not appear to be involved in binding itself, but may down-regulate the adhesion of memory but not naive CD4 T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antigen-independent adhesion of CD45RA (naive) and CD45RO (memory) CD4 T cells to B cells. 135 61

Infection with the human immunodeficiency virus (HIV) ultimately results in profound immunodeficiency characterized by severe depletion of CD4+ T helper cells. In symptomatic infection a general perturbance of immune function is observed. Here recent insights in the sequence of events in progression to AIDS is reviewed. Following seroconversion a rapid persistent loss of inducible B cell function is observed. In addition, in long term infection, antigen-presenting cell functions of monocytes and dendritic cells are increasingly affected. T-cell non-responsiveness, preceding CD4 cell loss, appears to be induced through several different, sequential mechanisms. In early infection, the in-vivo deletion of memory cells can account for the in-vitro decreased responsiveness. Later on in infection, when the balance between memory and naive T cells is normalized, both CD4 and CD8 cells are non-responsive to nominal antigen and low dose anti-CD3 monoclonal antibodies. This anergy is at the level of IL-2 gene expression since early signal transduction events following CD2 and CD2 receptor occupancy are normal. This state of anergy, probably due to inappropriate activation in vivo, may be related to programmed cell death (PCD) observed in vitro for both CD8 and CD4 cells reflecting a systemic interference with maturation and differentiation of T cells. In progression to symptomatic infection, the proportion of non-responsive CD8 cells with immature or activated phenotypes increases and in about fifty percent of the cases, CD4 cell decline may accelerate in association with emergence of syncytium-inducing HIV variants. During this progressive stage, anti-CD3 reactivity is severely decreased, and alloantigen reactivity and finally the capacity to respond to phytohemagglutinin (PHA) are affected. These functional parameters appear useful for staging of HIV-infected individuals and for evaluation of anti-viral therapy.
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PMID:Immunological abnormalities in the natural history of HIV infection: mechanisms and clinical relevance. 135 68

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
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PMID:Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein. 135 46

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells.
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PMID:T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. 151 49

Peripheral B cells from six patients affected with the hyper-IgM immunodeficiency syndrome, characterized by an absence of IgG and IgA in serum with a concomitant elevated level of IgM, were analyzed for phenotypic and functional characteristics. We report that although the membrane antigenic pattern expression was characteristic of mature B cells, B cells from most patients exhibited an impairment in their in vitro response to several lymphokines, such as recombinant interleukin 2 (rIL-2) and low molecular weight B-cell growth factor (BCGF), that induce proliferation of anti-mu-activated B cells. This impairment was also found in response to a lymphokine mixture from a CD2-activated T-cell clone. The decrease in lymphokine-induced B-cell proliferation was accompanied by a low B-cell differentiation, whether patients' B cells were stimulated by the T-cell clone supernatant or rIL-2 and rIL6, lymphokines able to support differentiation of Staphylococcus aureus Cowan I (SAC)-activated B cells. In addition, none of the lymphokines tested were able to induce patients' B cells to switch from IgM-secreting cells to IgG- and IgA-secreting cells. We conclude that this syndrome is associated with a defect in lymphokine-dependent maturation of B lymphocytes, although the T- or the B-cell origin of the defect still cannot be determined.
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PMID:Hyper-IgM immunodeficiency syndrome: influence of lymphokines on in vitro maturation of peripheral B cells. 156 Jan 9

Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.
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PMID:Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS). 156 29

We describe an infant whose peripheral blood mononuclear cells were unable to proliferate or synthesize IL-2 in response to a mitogenic combination of antibodies directed against CD2 and CD28. This peculiar defect, which has been stable to date, was attributed to an impairment in CD28-mediated T cell activation, because further comitogenic combinations containing anti-CD28 monoclonals also failed to induce normal proliferation of the patient's T cells. In contrast, proliferation after membrane stimulation (with anti-CD2, recombinant IL-2, or certain lectins) or transmembrane activation (with phorbol ester and calcium ionophore) was normal, suggesting that his lymphocytes did not have a general membrane or intracellular signalling impairment. A T cell line derived from the patient confirmed the existence of a severe defect in CD28-mediated T cell proliferation, but also showed a profound impairment in CD3-induced T cell proliferation. Other cell surface molecules like CD2 and CD25 were, in contrast, capable of transducing normal proliferation signals. As all relevant molecules were detectable by cytofluorography and immunoprecipitation, we conclude that the patient's lymphocytes had an intrinsic defect in the delivery of CD28-mediated signals which, in the absence of monocytes, also affected CD3-mediated proliferation. The study of this novel kind of immunodeficiency may help to unravel the complex interactions that take place among CD2, CD3 and CD28 during T cell activation. The presence of an idiopathic thrombocytopenia in the patient suggests the intriguing possibility of a role for CD28 in the maintenance of peripheral blood platelets levels, although alternative interpretations are not ruled out.
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PMID:Impaired T cell signal transduction through CD28 in a patient with idiopathic thrombocytopenia. 165 36

The Transfusion Safety Study retrospectively screened a repository of serum specimens collected in late 1984-early 1985 to identify blood donors with antibody to human T-cell lymphotropic virus (HTLV) at that time. They and their recipients have been traced for additional HTLV studies. Immunophenotypic analyses of peripheral blood lymphocytes from nine anti-HTLV-positive recipients, assumed to be infected during or since late 1984, showed no significant changes from healthy controls. Evaluation of the immunophenotypes of the 48 donors, however, showed significant elevations in the absolute counts of the T-cell (CD2) and natural killer (CD56) populations, the T helper/inducer and suppressor/inducer subsets (CD4+ CD29+ and CD4+ CD45RA+), and changes in T-cell activation markers. Long-term but not recent HTLV infection appears to alter the T-cell immunophenotypic pattern. Both infection with HTLV and human immunodeficiency virus type 1 are associated with a decreased CD2+ CD26+ count.
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PMID:Lymphocyte immunophenotypes among anti-HTLV-I/II-positive blood donors and recipients. The Transfusion Safety Study Group. 167 14

We report the consequences of low expression of the T cell receptor (TcR)/CD3 complex by T lymphocytes from a 4-year-old boy with a mild immunodeficiency. TcR/CD3 expression was found to be deficient on both resting and activated T cells, using both anti-CD3 and anti-TcR alpha/beta monoclonal antibodies. As shown by immunofluorescence and immunoprecipitation studies, residual expression (corresponding to about 10% of normal) was detectable on resting and activated TcR alpha/beta+ T cells. Other T cell membrane receptors were normally expressed. The functional consequences of this TcR/CD3 expression deficiency included an absence of T cell proliferation, interleukin 2 receptor expression and calcium flux following anti-CD3 and anti-CD2 antibody-triggered T cell activation. Antigen (tetanus toxoid, Candida and allogeneic cell)-induced proliferation was detectable. In contrast, cytotoxic T cell activity towards allogeneic cells was deficient. These findings shed light on the function of the TcR/CD3 complex and indicate that the expression of a limited number of TcR/CD3 receptors may be sufficient to trigger antigen-specific T cell activation (and, possibly, differentiation) and that anti-CD3 antibody-induced T cell activation differs somewhat from antigen/major histocompatibility complex molecule-induced activation. These results also confirm that the CD2 pathway of T cell activation is CD3 dependent.
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PMID:Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation. 167 69


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