Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 51, Issue 1 B76-B82, Copyright © 1996 by The Gerontological Society of America

JOURNAL ARTICLE

Reciprocal expression of P-glycoprotein and TAP1 accompanied by higher expression of MHC class I antigens in T cells of old mice

JM Witkowski, G Gorgas and RA Miller
Institute of Gerontology, University of Michigan, USA.

We have shown previously that (a) aging leads to an increase in the proportion of murine splenic T cells that express high activity of P- glycoprotein (PGP), the ATP-dependent plasma membrane pump that mediates multiple drug resistance, and (b) PGPhi CD4 memory cells from mice of any age do not proliferate or secrete IL-4 after activation with anti-CD3 and IL2. We now report that the age-associated increase in expression of MHC Class I molecules is limited to the subset of T cells that overexpress PGP and thus extrude the fluorochrome R123 (the "R123lo" subset). Although H-2 levels increase on T cells of old mice, the levels of TAP1, a component of the polypeptide pump responsible for assembly and internal transport of Class I MHC molecules, decline, unexpectedly, by about fourfold in T cells from old donors. Thus, aging leads to reciprocal changes in the level of T-cell expression of PGP and TAP1, two closely related members of the ABC superfamily of peptide transport proteins.


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