Reciprocal expression of P-glycoprotein and TAP1 accompanied by higher expression of MHC class I antigens in T cells of old mice.
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.
Institute of Gerontology, University of Michigan, USA.
J M
JM
Witkowski
G
G
Gorgas
R A
RA
Miller
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis*; D000375:Aging / Q000502:physiology*; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse