Скачать или смотреть Naive T cell activaton and proliferation map

Naïve T cells can respond to novel pathogens that the immune system has not yet encountered. Recognition by a naïve T cell clone of its cognate antigen results in the initiation of an immune response. In turn, this results in the T cell acquiring an activated phenotype seen by the up-regulation of surface markers CD25+, CD44+, CD62Llow, CD69+ and may further differentiate into a memory T cell.

Having adequate numbers of naïve T cells is essential for the immune system to continuously respond to unfamiliar pathogens.

Mechanism of activation[edit]
When a recognized antigen binds to the T cell antigen receptor (TCR) located in the cell membrane of Th0 cells, these cells are activated through the following "classical" signal transduction cascade:[2]

the tyrosine kinase Lck is activated, which results in phosphorylation of
the CD3 coreceptor complex and ζ-chains of the TCR and activation of the ζ-chain- associated protein Zap70
activated Zap70 in turn phosphorylates the membrane adaptor Lat, which subsequently recruits several Src homology domain–containing proteins, including phospholipase C-γ1 (PLC-γ1)
activation of PLC-γ1 results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 3,4,5-triphosphate and diacylglycerol
inositol 3,4,5-triphosphate triggers release of Ca2+ from intracellular stores and diacylglycerol activates protein kinase C and RasGRP
RasGRP in turn activates the mitogen-activated protein kinase cascade which
An alternative "non-classical" pathway involves activated Zap70 directly phosphorylating the p38 MAPK that in turn induces the expression of the vitamin D receptor (VDR). Furthermore, the expression of PLC-γ1 is dependent on VDR activated by calcitriol.[2] Naïve T cells have very low expression of VDR and PLC-γ1. However activated TCR signaling through p38 upregulates VDR expression and calcitriol activated VDR in turn upregulates PLC-γ1 expression. Hence the activation of naïve T cells is crucially dependent on adequate calcitriol levels.[2]

In summary, activation of T cells first requires activation through the non-classical pathway to increase expression of VDR and PLC-γ1 before activation through the classical pathway can proceed. This provides a delayed response mechanism where the innate immune system is allowed time (~48 hrs) to clear an infection before the inflammatory T cell mediated adaptive immune response kicks in.[2]