naive t cell naive t cell in immunology, a naive t cell (th0 cell) is a t cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. among these are the naive forms of helper t cells (cd4+) and cytotoxic t cells (cd8+). any naive t cell is considered immature and, unlike activated or 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 l-selectin (cd62l) and c-c chemokine receptor type 7 (ccr7); 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 (tscm, stem cell memory t cells; tmp, memory t cells with a naive phenotype), 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 (treg, regulatory t cells; rte, recent thymic emigrant). 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: the tyrosine kinase lck 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 (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. 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 (~48 hrs) to clear an infection before the inflammatory t cell mediated adaptive immune response kicks in.