Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls) in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.
Therapeutic anti-D immunoglobulin preparations issued by the Scottish National Blood Transfusion Service, between 1980 and 1986, were evaluated using in-vitro Fc-mediated functional tests that reflect potential in-vivo mechanisms of specific red cell destruction and clearance. All batches tested were found to: (a) contain anti-D of mainly IgG1 subclass and lesser amounts of IgG3; (b) mediate lymphocyte and monocyte rosetting; and (c) produce lytic activity in both K cell and monocyte ADCC. The functional activity of the therapeutic immunoglobulin preparations over this period of production had not altered despite increased plasma contributions latterly to the pool from deliberately immunized male donors. This is the first in-vitro study of the Fc-mediated function of therapeutic polyclonal anti-D preparations. As these preparations were clinically effective in the prophylactic anti-D programme, such bioassays of FcRI/II and FcRIII activity are justified for the future evaluation of immune plasma before blending for fractionation and production of therapeutic anti-D immunoglobulin.
Summary. The passive administration of anti‐D immunoglobulin is effective in preventing Rh alloimmunization and therefore preventing haemolytic disease of the newborn. However, diminishing availability and increased demand render an alternative source of anti‐D desirable. We report the production of two human monoclonal IgGl antibodies specific for Rhesus antigen D. Data are presented on the serological reactivity of these antibodies and on their ability to promote in vitro biological activity. Antibody derived from both lymphoblastoid cell lines and the hetero‐hybrid cell lines were compared for both ESD‐1 and ESD‐4. The ability of the antibodies to detect rhesus related antigens in animal tissue was also assessed. We present some evidence for altered reactivity of the ESD‐4 antibody following fusion of the lymphoblastoid parent line to a murine plasmacytoma.
Various natural products have been proposed to both increase health at the organismic level, and delay the onset of cellular aging. Of particular interest is resveratrol, a phytoalexin that has been demonstrated to have cardioprotective effects and to slow the progression of a variety of illnesses, including various types of cancers. More recently, resveratrol has been demonstrated to increase the maximum lifespan of model organisms, such as C. elegans, D. melanogaster and N. furzeri. However, the potential health benefits of resveratrol and other similar compounds on the human immune response have not been adequately addressed. We have, therefore, initiated research to determine the in vitro effects of the nutraceuticals resveratrol, and its analogs (polydatin and acetyl-resveratrol), as well as curcumin on a variety of human T cell functions. In this study we evaluated the effect of these compounds on proliferative potential, telomerase activity, expression of costimulatory and memory surface markers and sirtuin gene expression profiles of both human CD4 and CD8 T cells. Our data show that these compounds stimulated strong dose-dependent anti-inflammatory responses, and upregulated surface protein markers associated with the suppression of T cell activity. Our preliminary results suggest that these compounds may function to down-modulate ongoing CD4 and CD8 immune activity, while, nevertheless, poising the T cells for a subsequent immune response.
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