Immunological Consequences (immunological + consequence)

Distribution by Scientific Domains

Selected Abstracts

Progressive CD127 down-regulation correlates with increased apoptosis of CD8 T cells during chronic HIV-1 infection

Shu-Ye Zhang
Abstract Chronic HIV-1 infection can induce a significant decrease in CD127 expression on CD8 T cells, but the underlying mechanisms and immunological consequences are unclear. In this study, we investigated CD127 expression on CD8 T cells from a total of 51 HIV-1-infected subjects and 16 healthy individuals and analyzed the association between CD127 expression and CD8 T-cell apoptosis in these HIV-1-infected subjects. We found that CD127 expression on total CD8 T cells was significantly down-regulated, which was correlated with the increased CD8 T-cell apoptosis and disease progression of chronic HIV-1 infection. The in vitro addition of IL-7 efficiently rescued the spontaneous apoptosis of CD8 T cells from HIV-1-infected individuals. IL-7 stimulation also transiently down-regulated CD127 expression, whereas some of the CD127, CD8 T cells regained CD127 expression soon after IL-7 was retracted from the incubation medium. Thus, IL-7 stimulation reduced apoptosis of both CD127+ and CD127,CD8 T cells to some degree. These data indicate that CD127 loss might impair IL-7 signaling and increase CD8 T-cell apoptosis during HIV-1 infection. This study, therefore, will extend the notion that IL-7 could be a good candidate for immunotherapy in HIV-1-infected patients. [source]


EVOLUTION, Issue 2 2008
Kurt A. McKean
The evolution of immune function depends not only on variation in genes contributing directly to the immune response, but also on genetic variation in other traits indirectly affecting immunocompetence. In particular, sexual selection is predicted to trade-off with immunocompetence because the extra investment of resources needed to increase sexual competitiveness reduces investment in immune function. Additional possible immunological consequences of intensifying sexual selection include an exaggeration of immunological sexual dimorphism, and the reduction of condition-dependent immunological costs due to selection of ,good genes' (the immunocompetence handicap hypothesis, ICHH). We tested for these evolutionary possibilities by increasing sexual selection in laboratory populations of Drosophila melanogaster for 58 generations by reestablishing a male-biased sex ratio at the start of each generation. Sexually selected flies were larger, took longer to develop, and the males were more sexually competitive than males from control (equal sex ratio) lines. We found support for the trade-off hypothesis: sexually selected males were found to have reduced immune function compared to control males. However, we found no evidence that sexual selection promoted immunological sexual dimorphism because females showed a similar reduction in immune function. We found no evidence of evolutionary changes in the condition-dependent expression of immunocompetence contrary to the expectations of the ICHH. Lastly, we compared males from the unselected base population that were either successful (IS) or unsuccessful (IU) in a competitive mating experiment. IS males showed reduced immune function relative to IU males, suggesting that patterns of phenotypic correlation largely mirror patterns of genetic correlation revealed by the selection experiment. Our results suggest increased disease susceptibility could be an important cost limiting increases in sexual competitiveness in populations experiencing intense sexual selection. Such costs may be particularly important given the high intersex correlation, because this represents an apparent genetic conflict, preventing males from reaching their sexually selected optimum. [source]

Inhibition of the lymphotoxin pathway as a therapy for autoimmune disease

Jeffrey L. Browning
Summary: The lymphotoxin (LT) system is part of the tumor necrosis factor family and is required for lymph node development. It has provided a wonderful tool for the dissection of processes critical not only for lymphoid organ development but also the maintenance of the adult immune architecture and the formation of ectopic organized lymphoid tissues in chronically inflamed sites. A soluble lymphotoxin-, receptor-immunoglobulin (LT,R-Ig) fusion protein can block this pathway and is currently being tested in the treatment of autoimmune disease. This review focuses on the immunological consequences of combined LT and LIGHT inhibition with LT,R-Ig administration as distinct from the developmental biology. [source]

Natural killer cell cytotoxicity: how do they pull the trigger?

IMMUNOLOGY, Issue 1 2009
Nicola J. Topham
Summary Natural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery. [source]

The vitamin D slant on allergy

Matthias Wjst
Oral vitamin D supplementation has been introduced into modern medicine to prevent rickets without the knowledge that this may have profound immunological consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell maturation and consecutive Th1 cell development, which has independently described as a key mechanism of allergy development. Animal studies and epidemiological surveys now provide a first link of early vitamin D supplementation and later allergy where several vitamin D regulated genes seem to be involved. A randomized clinical trial of vitamin D supplementation could be a further step to follow up the vitamin hypothesis. [source]