Reciprocal expression of P-glycoprotein and TAP1 accompanied by higher expression of MHC class I antigens in T cells of old mice. J Gerontol A Biol Sci Med Sci 51

We have shown previously that (a) aging leads to an increase in the proportion ofmurine splenic T cells that express high activity of P-glycoprotein (PGP), the ATP-dependent plasma membrane pump that mediates multiple drug resistance, and (b) PGP1 " CD4 memory cells from mice of any age do not proliferate or secrete IL-4 after activation with anti-CD3 and IL-2. 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 "R1231" " 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 ofT-cell expression of PGP and TAP1, two closely related members of the ABC superfamily ofpeptide transport proteins. AGING in mice and humans is accompanied by shifts inL the proportions of phenotypically distinguishable T-cell subsets. The most prominent of these is the increase in the proportion of T cells expressing the antigenic profile characteristic of memory cells, as determined by expression of CD44, CD45RB, and MEL-14, and the corresponding decrease in the proportion of T cells with the phenotype o