title: Age-associated alterations in human natural killer cells. 2. Increased frequency of selective NK subsets.
abstract: We have analyzed the peripheral blood lymphocytes from healthy volunteers (20 to 94 years) for the expression of natural killer (NK) cell surface markers, NK activity, and B-cell proliferative response. An increase (2- to 3.5-fold) in relative percentage and absolute number of lymphocytes expressing Leu-7 (HNK-1) or Leu-11a (CD 16) antigen was found in the elderly group (greater than 80 years) as compared to young adults (less than 40 years). A two-color immunofluorescence analysis revealed that the age-associated increment was both progressive and selective; the actual increase occurred in Leu-7+11a+ and Leu-7+11a- populations (subsets with variable and weak NK activity) but not in the Leu-7-11a+ (most active) subset. There is a corresponding decrease in the 7-11a- cells. The ratios of 7+11a+/7-11a+ and 7+11a-/7-11a+ cells doubled with advancing age. Linear regression analysis suggests that the 7-11a+ cells are highly preserved through human senescence and the ratio of 7+11a- cells to the most stable subset, 7-11a+, could expand nearly 100-fold from birth to old age. Further analysis of Leu-7+ cells for the coexpression of Leu-11c (an epitope of Leu-11a) confirmed a similar pattern of changes in 7+11c+ and 7+11c- NK subsets with advancing age. The frequency of Leu-11+ (epitopes 11a+ or 11c+), but not of the subsets of 7+ phenotype (7+11a- or 7+11c-), correlates well with the NK activity (spontaneous killing of K562 tumor cell line). The 7+11c+ cells may directly or indirectly be responsible for the increase in NK activity observed with a majority of aged donors. The inverse relationship observed between the mitogenic response of lymphocytes to pokeweed mitogen (PWM) and the initial frequency of 7+11a-, but not other phenotypes, raises a potential functional significance for the expansion of the 7+11a-(7+11c-) subset. These age-associated NK phenotypic changes provide a cellular basis for our observations on age-associated increase in NK activity and decrease in mitogenic response to PWM.
authors: Department of Medicine, Evanston Hospital, Illinois 60201.
authors: R
authors: R
authors: Krishnaraj
authors: G
authors: G
authors: Blandford
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000145:classification; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D011043:Pokeweed Mitogens