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We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]

Genetic testing represents a major asset for discriminating between normal antigenic stimulation of B or T cells and malignant, pathological findings. The main difference between those two situations is the heterogenicity of lymphocyte populations as a result of diverse antigenic stimulation for the first situation, compared to single and identical population (clones) for the second situation. The present paper describes one of the many genetic assays capable of discriminating between normal and malignant, characterized by low time-to-result interval, accuracy, simplicity, and low cost comparing to other tests. [ABSTRACT FROM AUTHOR]

Currently, immunomodulation is an alternative in the fight against many diseases, being considered a possibility to fight against many infectious diseases that can affect pig herds. Selenium can be used for this purpose, the effect of its administration on the immune response being the main purpose of the present study. Following the administration of organic selenium, we found that in the case of WBC parameters, granulocytes and agranulocytes percentages and lymphoblastic transformation percentages of B lymphocytes, there are no major differences between the values recorded at the beginning of the experiment and the values recorded in the two experimental moments. Instead, following the administration of organic selenium, we observed significant increases in T lymphocytes percentages (by 9.94%, after 21 days, and respectively by 8.18%, after 30 days), percentages of lymphoblastic transformation of T lymphocytes (by 59.59% after 21 days, and respectively by 64.14% after 30 days), as well as the helper T lymphocytes/supressor T lymphocytes ratio (by 46.15% after 21 days, and respectively by 65.38% after 30 days). Regarding the percentage of B lymphocytes, a decrease of this parameter is observed by 38.34% after 21 days and by 21.84% after 30 days following the administration of the product based on organic selenium. [ABSTRACT FROM AUTHOR]

Background: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. Results: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization. This method, referred to as the Repertoire Dissimilarity Index (RDI), uses a bootstrapped subsampling approach to account for variance in sequencing depth, and, coupled with a data simulation approach, allows for direct quantification of the average variation between repertoires. We use the RDI method to recapitulate known differences in the formation of the CD4+ and CD8+ T cell repertoires, and further show that antigen-driven activation of naïve CD8+ T cells is more selective than in the CD4+ repertoire, resulting in a more specialized CD8+ memory repertoire. Conclusions: We prove that the RDI method is an accurate and versatile method for comparisons of immune repertoires. The RDI method has been implemented as an R package, and is available for download through Bitbucket. [ABSTRACT FROM AUTHOR]

This article presents abstracts for various research papers to be presented in the European Society for Dermatological Research's symposium on September 26-28, 1997. These research papers pertain to subjects like the eortic classification for primary cutaneous lymphomas, different prognosis between cutaneous and systemic lymphoproliferative disorders, parapsoriasis and early cutaneous T cell lymphoma, immunoglobulin gene rearrangement of pseudo B-cell lymphomas and prognostic significance of polymerase chain reaction detectable dominant T lymphocyte clones.

Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20-90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34% and 46%, exhibited no detectable change in 56% and 47% and increased in 10% and 7% of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naıve cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naïve T-cell percentage and changes in health conditions. [ABSTRACT FROM AUTHOR]

Abstract: Many previous studies have described differential responses to mutagens among human lymphocyte subpopulations. However, there are some confusing data about the sensitivity to mutagens among lymphocyte subpopulations. In this paper we review the studies published to date reporting differential responses among CD4+ T-cells, CD8+ T-cells, B-cells and NK-cells exposed to different mutagens, using different assay methods, such as micronuclei (MN), sister chromatid exchanges (SCEs), single cell gel electrophoresis (SCGE), and fluorescence-activated cell sorting (FACS). These methods are mostly used for genetic biomonitoring of human populations exposed to potential mutagens. Thus, this review may provide a reference of target cells sensitive to mutagens that will be useful for genetic biomonitoring of human populations. [Copyright &y& Elsevier]

Decisions by uncommitted cells to differentiate down one lineage pathway or another is fundamental to developmental biology. In the immune system, lymphocyte precursors commit to T- or B-cell lineages and T-cell precursors to CD4 or CD8 independently of foreign antigen. T and B cells must also decide whether or not to respond to antigen and when a response is initiated, what sort of response to make such as the type of antibody, CD4 or CD8, and CD4 Th1 or Th2. The two basic mechanisms for these decision-making processes are selection and instruction. Selection depends on prior stochastic production of precommitted cells, which are then selected to respond by an appropriate signal; for example, CD8 and CD4 responses selected by peptide presented in association with major histocompatibility complex class I or II. In contrast, instruction occurs when an uncommitted precursor embarks upon a differentiation pathway in response to a particular set of signals; for example, Th1 and Th2 lineage commitment. In this paper, the signals that determine Th1 and Th2 differentiation are examined with a mathematical model and shown to act as a bistable switch permitting either Tbet or Gata3 to be expressed in an individual cell but not both. The model is used to show how the Tbet Gata3 network within an individual cell interacts with cytokine signals between cells and suggests how Th1 and Th2 lineage commitment can become irreversible. These considerations provide an example of how mathematical models can be used to gain a better understanding of lymphocyte differentiation in an immune response.Immunology and Cell Biology (2007) 85, 300–305; doi:10.1038/sj.icb.7100060; published online 1 May 2007 [ABSTRACT FROM AUTHOR]

Background Comparable T cell-containing and T cell-depleted culture systems for human IgE synthesis arc currently not available. Objective This has prompted us to develop peripheral blood mononuclear cell (PBMC) based culture systems for human IgE synthesis in the presence and absence of T cells. Methods In this paper we describe simplified conditions for in vitro synthesis of high levels of IgE by human peripheral blood B cells, both in T cell-containing cultures and in anti-CD40 stimulated T cell-depleted cultures. Results T cell-depleted cultures released approximately 20 times more IgE [range 4I0-2220ng/mL (mean 1270 ng/mL); based on six experiments using cells from three donors] than did T cell-containing cultures [range 23-105 ng/mL (mean 58ng/mL); based on 15 experiments using cells from three donors]. Reconstitution experiments were performed lo investigate the role of T cells on IgE synthesis. Adding T cells back to the anti-CD40 stimulated T cell-depleted cultures resulted in a dose-dependent inhibition of IgE production. In the absence of anti-CIMO low numbers of T cells stimulated, while high numbers suppressed, IgE production: the optimal ratio of T cells to non-T cells for maximal IgE production was found to be 1:1. At this ratio, irradiated (non-replicating) T cells supported a much greater IgE synthesis than did non-irradiated T cells. Conclusion The development of these systems provides directly comparable T cell-containing and T cell-depleted cultures for human IgE synthesis from peripheral blood, allowing further study of the role of T cells in IgE regulation. These systems will also be of use for determining whether potential modulators of IgE synthesis act on the T cells or on other cell types. [ABSTRACT FROM AUTHOR]

Freshly isolated B cells from chronic lymphocytic leukaemia patients (B-CLL) have been previously shown to induce a strong proliferative response and high levels of NK-like activity in lymphocytes from healthy donors. The present paper deals with the origin, mitotic state, target spectrum and cell surface phenotype of the NK-like effectors generated after stimulation with B-CLL. Experiments using large granular lymphocytes (LGL) and T cells as responders demonstrated that most of the precursors of the newly generated NK-like effectors express the CD3 antigen. The induction of NK-like activity paralleled cell activation, as judged by blast transformation, thymidine uptake and appearance of cell surface activation markers. The newly generated NK-like effectors displayed a T cell phenotype and a broader target repertoire than native NK cells. [ABSTRACT FROM AUTHOR]

Mitogen-transformed human peripheral blood lymphocytes and tonsil blasts were examined by rosette formation to detect the presence of membrane-bound immunoglobulin (Ig) and surface receptors for fixed IgG and fixed C3. In addition, the capacity of these cells to rosette with sheep erythrocytes was evaluated as a reaction characteristic of T lymphocytes. In order for clear morphological recognition of the rosetting transformed lymphocytes and the rosetting tonsil blasts a cytocentrifuge technique was developed and used in conjunction with autoradiography and/or with Romanowsky stains. Using these techniques and the culture methods described in this paper phytohaemagglutinin, pokeweed mitogen, streptococcal filtrates and purified protein derivative stimulated predominantly T cells in the peripheral blood of man. A minority of the transformed cells in these mitogen-stimulated cultures (<24%) did rosette with B lymphocyte markers and presumably represent a B-cell response. No significant differences were found between the T- or B-cell specificity of the mitogens investigated. Lymphoid preparations from tonsils excised from normal donors with recurrent tonsillitis were found to contain 6-15% lymphoblasts and the iarge majority of these cells formed rosettes with the B-cell markers, less than 20% of these lymphoblasts formed spontaneous sheep erythrocyte rosettes. Using a mixed rosetting technique a small proportion (<5%) of PHA-transformed cells and tonsil lymphoblasts were found to have combined sheep Fc or combined sheep C3 receptors. The investigation of B- and T-lymphocyte surface markers on mitogentransformed lymphocytes was extended to neopiastic lymphocyte populations and it was found that the majority of transformed cells (>70%) present in chronic lymphocytic leukaemia cultures stimulated with PHA after 6 days incubation were transformed T lymphocytes. [ABSTRACT FROM AUTHOR]