ArrayExpress Uploader07102no activationC57BL6Nno activationC57BL6Nno activationC57BL6Nno activationpLck-hCD1dTgno activationpLck-hCD1dTgno activationpLck-hCD1dTgactivated in vitro for 6 hoursC57BL6Nactivated in vitro for 6 hoursC57BL6Nactivated in vitro for 6 hoursC57BL6Nactivated in vitro for 6 hourspLck-hCD1dTgactivated in vitro for 6 hourspLck-hCD1dTgactivated in vitro for 6 hourspLck-hCD1dTgarrayexpress_sid6CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells...23427253E-GEOD-42835/profile/8773/arrayexpressuploader212cellperipheralthymustyrosineDec.12, 2014Falseexpression-data-of-hepatic-inkt-cells-from-plck-hcE-GEOD-42835_A-AFFY-45Expression data of hepatic iNKT cells from pLck-hCD1d transgenic miceNov.12, 2014CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery. Hepatic iNKT cells from wild-type and transgenic mice (expressing hCD1d molecule under the pLck promoter)http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-42835mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-42835/samples/