Biomedical subjects

L D Christensen

Publications and source records attributed to L D Christensen.

23 records · Page 2Linked to original sources

PubMed1989

Interleukin 2 receptor expression by human blood lymphocytes after vaccination with pneumococcal polysaccharides.

Proliferative responses of unseparated peripheral blood mononuclear cells (PBMC) and blood T cells to recombinant interleukin 2 (rIL-2) were significantly increased 7-21 days after the vaccination with pneumococcal polysaccharides (PPS). In contrast, non-T cells expressed increased responsiveness to rIL-2 only on post-vaccination day 7. Analysis of the proliferative response to rIL-2 among lymphocyte subsets (CD4+Leu8+, CD4+Leu8-, CD8+Leu8+, CD8+Leu8-, CD20+) in cultures of unseparated PBMC revealed that the CD8+Leu8- T cells expressed increased responsiveness 7-14 days after vaccination, whereas neither CD4+ (Leu8+ and Leu8-) nor CD8+Leu8+ T cells showed significantly increased responsiveness after vaccination. The CD20+ B cells, like non-T cells, expressed increased responsiveness to rIL-27 days after the vaccination only. Expression of the 55 kD low-affinity interleukin 2 receptor (IL-2R, CD 25) on freshly isolated PBMC, as judged by direct fluorescence staining with a MoAb anti-55 kD chain, was low (less than 3%) and an increased expression of this receptor was not detected following vaccination. In contrast, binding of 125I-labelled IL-2 to freshly isolated PBMC increased following vaccination (day 7). Scatchard plot analysis revealed a modest increase in the expression of high-affinity IL-2R (Kd = 1-2 pM), whereas the increase in expression of the 75-kD, intermediate-affinity IL-2R (Kd = 300 pM) was more pronounced (from 195 to 295 (means) receptors per PBMC). It is concluded that, following vaccination with PPS increased IL-2R expression is induced on blood lymphocytes. These investigations suggest a role for T cells in the human immune response against PPS.

Adult↗

PubMed1988

Interleukin 1-induced down-regulation of antibody binding to CD4 molecules on human lymphocytes.

Interleukin 1 (IL-1) is involved in the early activation of T lymphocytes. The CD4 antigen, described as a phenotypic marker of helper T cells, is also important in early T-cell activation by its ability to bind to MHC class II molecules on antigen-presenting cells, and to transmit positive (and negative) signals to the cells. We observed that purified human monocyte IL-1 as well as recombinant IL-1 alpha and IL-1 beta selectively decreased the binding of monoclonal antibodies to CD4 on the surface of otherwise unstimulated blood T cells, in contrast to prestimulated and continuously grown CD4+ cells. Under optimal growth conditions, the initial reduction in antibody binding to CD4 was followed by an apparent re-expression of the CD4 antigen even in the presence of high concentrations of IL-1. This re-expression did not occur if the cells were cultured at 4 degrees C, or after treatment with actinomycin D or cytochalasin B, indicating that protein synthesis and intact microfilament function were essential for re-expression of CD4 binding. The mechanism by which CD4 molecules are physically and/or functionally modulated by IL-1 is unclear.

Antibodies, Monoclonal↗

PubMed1988

Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases.

This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference in the effect of proteases on CD4- and CD8-positive cells. To determine the effect of proteases on interleukin-2 (IL-2)-induced cell proliferation, the proteases and IL-2 were added to the IL-2-dependent CTLL-2 cell line. AP and ELA inhibited the proliferation of these cells. When IL-2 was added in excess, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due to cleavage of IL-2.

Binding, Competitive↗

PubMedDate not supplied

Natural killer cells lack ecto-5'-nucleotidase.

Ecto-5'-nucleotidase (ecto-5'-NUC, EC 3.1.3.5., CD73) is a plasma membrane enzyme, which catalyzes the hydrolytic dephosphorylation of purine nucleotides to the corresponding nucleosides so that they can pass through the plasma membrane. The distribution of ecto-5'-NUC is heterogeneous, but all blood mononuclear cell (BMC) subpopulations investigated until now have had ecto-5'-NUC activity. Purified natural killer (NK) cells were prepared by fluorescence-activated cell sorting of CD16-positive cells (purity 94%). In purified NK cells the ecto-5'-NUC activity was less than 1 U/10(6) as estimated by a radioisotope method. Using a cytochemical assay, the proportion of cells with activity was less than 1%. The most likely explanation is that NK cells have no ecto-5'-NUC activity and that the very small ecto-5'-NUC activity observed in this study was caused by contaminating non-NK cells. NK cells thus constitute the only BMC subset known without ecto-5'-NUC activity.

5'-Nucleotidase↗

PubMedDate not supplied

Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis.

The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE) antibody identified a subgroup of CD14+ cells which contained all the elastase activity and which could be blocked by a specific chloromethylketone elastase inhibitor. By anti-CD14 labelling the HLE positive cells were identified as monocytes and amounted to 88% of this cell type (median: range 72-96%). In a parallel study of patients with active rheumatoid arthritis (RA) and control donors the elastolytic capacity of PMA-stimulated live MNC was higher for RA patients than for controls (p less than 0.02). For control donors the number of HLE+ cells correlated well to the elastolysis in the same MNC sample (Spearman's rho:0.83, p less than 0.05); in the samples from RA patients no correlation was found between the normal number of HLE+ cells and the increased elastolysis (rho: 0.54, p greater than 0.20).

Adult↗