Singularities of calcium signaling in effector T-lymphocytes

CD4(+) helper T (Th) lymphocytes orchestrate the immune response and include several types of effectors such as Thl, Th17 and Th2 cells. They fight against intracellular, extracellular pathogens and parasites respectively. They may also cause distinct immunopathological disorders. Thl and Th17 are implicated in the development of autoimmune diseases while Th2 cells can initiate allergic diseases. These subsets differ by their TCR-associated signaling. In addition, the regulation of intracellular calcium concentration is not the same in Th1, Th2 and 17 cells. Our group showed that Th2 cells selectively overexpressed voltage-activated calcium (Ca(v)1)-related channels. An increasing number of groups report the presence of Ca(v)1 -related products in T-lymphocyte subsets. This is a matter of debate since these calcium channels are classically defined as activated by high cell membrane depolarization in excitable cells. However, the use of mice with ablation of some Ca(v)1 subunits shows undoubtedly an immune phenotype raising the question of how Ca(v)1 channels are regulated in lymphocytes. We showed that knocking down Ca(v)1.2 and/or Ca(v)1.3 subunits impairs the functions of Th2 lymphocytes and is beneficial in experimental models of asthma, while it has no effect on Th1 cell functions. Beyond the role of Ca(v)1 channels in T-lymphocytes, the identification of key components selectively implicated in one or the other T cell subset paves the way for the design of new selective therapeutic targets in the treatment of immune disorders while preserving the other T-cell subsets. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. 2012 Elsevier B.V. All rights reserved.