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- Title
Calcium dependence of T cell proliferation following focal stimulation.
- Authors
Schwarz, Eva C.; Kummerow, Carsten; Wenning, Anna S.; Wagner, Kerstin; Sappok, Anne; Waggershauser, Katherina; Griesemer, Désirée; Strauß, Bettina; Wolfs, Melodie-Jo; Quintana, Ariel; Hoth, Markus
- Abstract
Clonal T cell expansion through proliferation is a central process of the adaptive immune response. Apoptosis of activated T cells is required to avoid chronic inflammation. T cell proliferation and apoptosis are often analyzed with stimuli that do not induce formation of a functional immunological synapse. Here we analyze the Ca dependence of proliferation and apoptosis in primary human CD4 T cells following stimulation with anti-CD3/anti-CD28-coated beads, which induce a tight interaction similar to the immunological synapse. We found this focal stimulation to be much more efficient for stimulating IL-2 production and proliferation than non-focal TCR stimuli. Surprising little Ca entry through Ca channels was required for T cell proliferation. Transient free intracellular calcium concentration ([Ca]) elevations of up to 220 nM from a baseline level of around 40 nM were sufficient for maximal proliferation in primary human CD4 T cells. We also show that proliferation was very Ca sensitive in the range 90-120 nM, whereas apoptosis was basically constant for [Ca] levels of 90-120 nM. We conclude that very small changes in [Ca] can dramatically change the ratio between proliferation and apoptosis, thus keeping the balance between overshooting and inefficient immune responses.
- Publication
European Journal of Immunology, 2007, Vol 37, Issue 10, p2723
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200737039