[The Role of Extracellular Calcium Ions Reduction in T Cell Activation in Human Peripheral Blood]

Calcium plays a fundamental role in many essential live functions. It is well-known that many infections can lead to hypocalcaemia in humans. The importance of extracellular calcium concentration ([Ca2+]o) in T-cell activation is well recognized, but [Ca2+]o levels necessary for lymphocyte activation have not been investigated in detail. Whole blood from healthy donors was stimulated by immobilized anti-CD3 plus soluble co-stimulation anti-CD28 mAb and activation parameters have been analyzed. Interleukins-2 (IL-2), JL-4, IL-17A, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production and CD4+CD69+, CD4+CD25+, CD4+(CYTOKINE)+ T cells were used as activation parameters. To change current [Ca2+]o values in PB we used EGTA. No EGTA influence on resting T cells was shown. Dependences of T-cell activation parameters on various [Ca2+]o were studied. These data indicate that extracellular Ca2+ chelation by EGTA leads to non-linear dependences of T-cell activation parameters on [Ca2+]o values. Obtained dependence of the number of CD4+CD69+ T cells from EGTA can be represented as a nonlinear curve with two distinct peaks. Cytokines production by activated Th1, Th2 and Th17 cells and CD4+(CYTOKINE)+ T cells have been analyzed in dependence on EGTA. The first peak is close to the norm-pathology border. The second peak is in the pathological [Ca2+]o values of PB. However, the local minimum between them is entirely in the "pathological" range. Obtained dependences can be represented as a nonlinear curve with two distinct peaks. All dependences shape have similar curve describing the influence of [EGTA] values on activated CD4+CD69+ T cells. Physiological significance of obtained data discussed.