Developmentally regulated expression of P-glycoprotein (multidrug resistance) activity in mouse thymocytes

P-glycoprotein (P-gly) is the transmembrane efflux pump responsible for multidrug resistance in tumor cells. The activity of P-gly in mature peripheral lymphocytes is lineage specific, with CD8⁺ T cells and natural killer (NK) cells expressing high levels as compared to CD4⁺ T cells and B cells. We have now investigated P-gly activity in immature and mature subsets of mouse thymocytes. Our data indicate that P-gly activity is undetectable in immature CD4^?8^? and CD4⁺8⁺ thymocyte subsets. Among mature thymocytes, P-gly activity is absent in the CD4⁺ subset but present in the more mature (HSA^low) fraction of CD8⁺ cells. Furthermore, while thymic CD4^?8^? T cell receptor (TCR) γδ cells have little P-gly activity, a minor subset of CD4^?8^? or CD4⁺ TCR αβ⁺ thymocytes bearing the NK1.1 surface marker expresses high levels of P-gly activity. Collectively, our results indicate that P-gly activity arises late during thymus development and is expressed in a lineage-specific fashion.