Calcium dependence of T cell proliferation following focal stimulation.
Eur J Immunol
; 37(10): 2723-33, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17899547
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(2+) 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(2+) entry through Ca(2+) channels was required for T cell proliferation. Transient free intracellular calcium concentration ([Ca(2+)](i)) 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(2+) sensitive in the range 90-120 nM, whereas apoptosis was basically constant for [Ca(2+)](i) levels of 90-120 nM. We conclude that very small changes in [Ca(2+)](i) can dramatically change the ratio between proliferation and apoptosis, thus keeping the balance between overshooting and inefficient immune responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T CD4-Positivos
/
Cálcio
/
Proliferação de Células
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha