Words similar to intrathymic
Example sentences for: intrathymic
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The relatively short kinetics of surface CD4 down-regulation and the delayed CD8 surface disappearance can be interpreted as a PKC-mediated selection signaling in favor of CD8 +CD4 -/α:β-TCR cells that may operate during intrathymic T cell differentiation.
The fundamental reasons for the design of our ex-vivo experiments are three-fold: (a) The need to evaluate intrathymic differentiation as close as it could be physically possible to an in vivo model; (b) We sought to perform the experiments on "untouched" cells with the least of manipulations.
It is conceivable that a similar mechanism might be used by extra-cellular signals in the thymic epithelium during intrathymic differentiation.
It is known that during clonal selection in the thymus, immature CD4, CD8 double positive cells develop into single positive CD4 or CD8 cells according to the relative affinity of their TCR to class II or class I molecules respectively [ 5 6 ] . These immature T-cells are selected in the thymic epithelium on the basis of their TCR interaction with either class I or class II MHC molecules [ 7 8 ] , thus generating two mutually exclusive subpopulations that are characterized by the expression of either CD4 or CD8 glycoproteins [ 9 ] . Earlier studies in the murine system have demonstrated that PMA and cAMP can modulate the expression CD4 and CD8 on developing thymocytes [ 10 11 12 13 ] . In keeping with these findings, ex vivo experiments with human thymocytes previously reported by our group, revealed that while phorbol esters can coordinately regulate the transcription of α and β TCR during intrathymic T cell differentiation [ 14 ] , cAMP selectively affected the transcription of the α and δ-TCR [ 15 16 ] . Together the murine data and our own findings support the hypothesis that in humans, TCR expression and CD4, CD8 commitment and selection may be regulated by the same signal-transduction pathways.
Since (a) it is generally accepted that CD4 or CD8 are physically associated to the TCR in the course of T cell activation [ 17 18 ] and (b) it is well known that mitogen activated protein (MAP) kinase signaling is involved in the selection of the T cell repertoire [ 19 20 ] , the present study further proposes that the PKC and PKA-mediated signaling, which regulates TCR expression, can coordinately modulate the selection of CD4 +CD8 -and CD4 -CD8 +T cells during human intrathymic differentiation.
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