Interleukin 2 receptor expression by T cells in human aging.
Aged individuals have depressed cell-mediated immunity and diminished T cell proliferation to mitogenic and antigenic stimuli. Because T cell responses depend on the surface expression and normal function of interleukin 2 receptors, we measured the quantities and affinities of cell surface IL-2R and the amount of soluble IL-2R alpha chain (p55) release in vitro in PHA-stimulated mononuclear cells from healthy aged (greater than or equal to 65 years old) and young (less than or equal to 39 years old) donors. At the peak of the PHA response, the fraction of cells expressing IL-2R alpha chain (CD25+) was lower in the aged (43% vs 56%, P = 0.033). Relative to the lower proliferation and CD25 expression, old donor cells released unexpectedly high quantities of soluble alpha chain into culture supernatants. However, the average affinities and the mean numbers of high- and low-affinity surface receptors per CD25+ cell were equivalent in cells from eight pairs of aged and young donors (1850 vs 1586 high affinity, and 20,655 vs 23,466 low affinity, P greater than 0.2 for both). The soluble IL-2R released by stimulated cells had no effect on proliferative responses, because addition of saturating doses of exogenous recombinant IL-2 did not increase cellular proliferation, and addition of soluble anchor-minus recombinant IL-2R alpha chain did not suppress it. These results indicate that in healthy older individuals, diminished numbers of T cells can be induced to express cell surface IL-2R following mitogenic stimulation, although aged CD25+ can express a normal complement of IL-2R molecules. In the aged, either CD25+ cells release excessive quantities or a subset of cells synthesizes and releases soluble IL-2R alpha chain into the extracellular environment without expressing it on the cell surface.
Orson
F M
FM
Department of Internal Medicine, Baylor College of Medicine, Houston, Texas.
Saadeh
C K
CK
Lewis
D E
DE
Nelson
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2