Naive T cells are commonly characterized by the surface expression of L-selectin and C-C Chemokine receptor type 7 ; the absence of the activation markers CD25, CD44 or CD69; and the absence of memory CD45RO isoform. They also express functional IL-7 receptors, consisting of subunits IL-7 receptor-α, CD127, and common-γ chain, 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. 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. For instance, some non-naive T cells express surface markers similar to naive T cells, some antigen-naive T cells have lost their naive phenotype, and some T cells are incorporated within the naive T cell phenotype but are a different T cell subset. 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.
the tyrosine kinaseLck which is associated with co-receptors CD4 and CD8: is engaged to phosphorylate the CD3 coreceptor complex and ζ-chains of the TCR and to recruit and activate 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
An alternative "non-classical" pathway involves activated Zap70 directly phosphorylating the p38 MAPK that in turn induces the expression of the vitamin D receptor. Furthermore, the expression of PLC-γ1 is dependent on VDR activated by calcitriol. 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. 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 to clear an infection before the inflammatory T cell mediated adaptive immune response kicks in.
