SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term culture identifies human profilin-1 as a potential bio-marker of immunosenescence

Background  

The adaptive immune response requires waves of T-cell clonal expansion on contact with pathogen and elimination after clearance of the source of antigen. However, lifelong persistent infections with common viruses cause chronic antigenic stimulation which takes its toll on adaptive immunity in late life. Chronic antigenic stress results in deregulation of the T-cell response and accumulation of anergic cells. Longitudinal studies of the elderly show that this impacts on survival. Identifying the nature of the defects in chronically-stimulated T-cells and protein bio-markers of these dysfunctional cells would help to understand age-associated compromised T-cell function (immunosenescence) and facilitate the development of targeted intervention strategies.     

Lymphokine release, suppressor cell generation, cell surface markers, and cytotoxic activity in cancer patients receiving natural interleukin-2

We monitored patients treated for 5 days with continuous infusion of increasing doses (3 to 6 x 10(6) U/d) of natural interleukin-2 (IL-2). CD16+, CD25+, and CD56+ cells increased after treatment. Plasma tumor necrosis factor-alpha (TNF-alpha) levels, but not interferon-gamma (IFN-gamma) levels, increased during IL-2 treatment, but spontaneous and IL-2-stimulated TNF-alpha secretion in vitro remained abnormally low. However, mitogen-stimulated TNF-alpha release was normal. Mitogen-stimulated, but not IL-2-stimulated, IFN-gamma release was strongly depressed. Low spontaneous and IL-2-stimulated cytotoxicity on K562 or Daudi increased after treatment. Low suppressor cell generation also normalized after treatment. This appears to be the first reported study of immunologic monitoring of cancer patients treated with natural rather than recombinant IL-2.     

The European searchable tumour line database

The European Searchable Tumour line Database (ESTDAB) () is a freely available and fully searchable database of melanoma-derived cell lines, which have been characterised for over 250 immunologically relevant markers by a consortium of European scientists. The database is linked to a cell bank, which can provide melanoma cell lines to non-profit investigators for a nominal handling charge. All cells are fully HLA typed at the genomic and surface expression levels. The expression of a number of surface antigens, apoptotic markers, tumour-associated antigens and extracellular matrix proteins has also been determined. Cytokine secretion has been tested and polymorphisms in cytokine genes have been identified. Glycans at the cell surface were identified and glycosyltransferase activity quantified. Cell lines with a particular constellation of these parameters can be sought online via the ESTDAB interface, which is included as part of the Immuno-Polymorphism Database (IPD) section of the European Bioinformatics Institute’s (EBI) website. This paper is a focussed research review from the meeting which took place on the 28th–29th May 2008 in Nottingham, UK, celebrating the contribution of Prof. I.A. “Tony” Dodi (29.1.2008) to the EU project “Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumour immunology (ENACT).”     

Campylobacter jejuni 72Dz/92 cjaC gene coding 28 kDa immunopositive protein, a homologue of the solute-binding components of the ABC transport system

Screening of the Campylobacter jejuni 72Dz/92 cosmid gene bank enabled identification of the cjaC ( Camp. jejuni antigen C) gene encoding a highly immunogenic protein of apparent molecular mass 28 kDa. Gene bank searches indicated significant overall homology of the cjaC gene product, mainly to the Gram-negative periplasmic solute-binding proteins of the ABC transport system which recognize polar amino acids and opines. CjaC protein contains the motif LVAC at the end of the putative 19 amino acid signal sequence, which suggests that it might be a lipoprotein. In the 5' flanking region of the cjaC gene, two potential promoter regions were observed. The cjaC gene is conserved among some isolates of three serotypes commonly isolated from humans (HL serotypes 1,4,71).