Effect of Kv1.3 inhibition on T cell development, activation and signaling (135.23)
| Autor: | Jason Rosenzweig, Lori Lebson, Justin Mancini, Peter Calabresi, Katharine Whartenby |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:135.23-135.23 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.184.supp.135.23 |
| Popis: | The voltage-gated potassium channel Kv1.3 is highly expressed in effector memory T cells (TEM) but not in central memory (TCM ) or naïve T cells. TEM are pathogenic in several autoimmune diseases. Acute blockade of Kv1.3 by the sea anemone toxin ShK reduces activation induced proliferation of TEM. However, in Kv1.3-/- mice, in which the gene was absent from development, no immune system defects were found, which was attributed to compensatory channels (Koni et al. JBC, 2003). The limitations of pharmacological blockade and gene-targeted deletion led us to develop a lentiviral system to co-express a dominant negative Kv1.3 and GFP. We have been using this lentivirus to query the role of Kv1.3 both in the development and activation of T cells. We have conducted studies in which we have suppressed channel expression in the development of T cells from a gene-modified bone marrow transplant and also assessed the impact of blocking channel expression during antigen-specific activation of CD4+ T cells. Using the antigen specific mouse system allows multiple advantages over previous studies including the feature that specific T cells can be tracked and monitored and compared to unmodified T cells. Initial results showed that Kv1.3-silenced CD4+ T cells skewed towards the TCM phenotype. We will report on our additional results using this lentiviral expression system, which is allowing us to study the role of Kv1.3 in T cells in mice and its effect on signaling pathways. |
| Databáze: | OpenAIRE |
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