T cell which has not yet encountered its cognate antigen
In
memory T cells, has not encountered its cognate
antigen within the periphery. After this encounter, the naive T cell is considered a mature T cell.
Phenotype
Naive T cells are commonly characterized by the surface expression of
CD132. In the naive state, T cells are thought to require the common-gamma chain cytokines
IL-7 and
IL-15 for homeostatic survival mechanisms.
[3] While naive T cells are regularly regarded as a developmentally synchronized and fairly homogeneous and quiescent cell population, only differing in T cell receptor specificity, there is increasing evidence that naive T cells are actually heterogeneous in phenotype, function, dynamics and differentiation status, resulting in a whole spectrum of naive cells with different properties.
[2] For instance, some non-naive T cells express surface markers similar to naive T cells (Tscm, stem cell memory T cells;
[4] Tmp, memory T cells with a naive phenotype
[5]), some antigen-naive T cells have lost their naive phenotype,
[6] and some T cells are incorporated within the naive T cell phenotype but are a different T cell subset (
Treg, regulatory T cells; RTE, Recent Thymic emigrant).
[2] It is important to appreciate these differences when assessing naive T cells. Majority of human naive T cells are produced very early in life when infant's thymus is large and functional. Decrease in naive T cell production due to involution of the thymus with age is compensated by so called "peripheral proliferation" or "homeostatic proliferation" of naive T cells which have emigrated from the thymus earlier in life. The homeostatic proliferation causes change to naive T cell gene expression and i.e. is manifested by acquisition of CD25 surface protein expression.
Function
Naive T cells can respond to novel pathogens that the immune system has not yet encountered. Recognition by a naive 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 naive T cells is essential for the immune system to continuously respond to unfamiliar pathogens.
Mechanism of activation
Main article:
T cell activation
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:
[7]- the tyrosine kinase
Zap70
- activated Zap70 in turn phosphorylates the membrane adaptor (PLC-γ1)
- activation of PLC-γ1 results in the hydrolysis of
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
vitamin D receptor (VDR). Furthermore, the expression of PLC-γ1 is dependent on VDR activated by
calcitriol.
[7] Naive 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 naive T cells is crucially dependent on adequate calcitriol levels.
[7]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.[7]
See also
Notes and references
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