Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency.
Previous studies from our laboratory have suggested that aging leads to an accumulation of cells expressing high levels of CD44, thought to be a marker for memory lymphocytes, and that positively selected CD44hi T cells, from mice of any age, respond poorly to concanavalin A (Con A) in limiting dilution estimates of interleukin (IL)-2-producing cells. We now report the results of a more comprehensive analysis of memory T cell function, in old and young mice, to non-cognate activators (Con A and the staphylococcal enterotoxin SEB). We report that memory T cells, isolated by removing cells bearing the CD45RB determinant, contain very few cells able to respond to either Con A or SEB under limiting dilution culture conditions, whether the responses are measured by IL-2 or by IL-3 accumulation. As a control, we show that memory T cells do respond strongly, at limiting dilution, to recently encountered priming antigens, i.e. Schistosoma mansoni egg antigen; the limiting dilution culture protocol thus does not preclude activation of memory T cells when cognate stimuli are presented to antigen-specific cells. These data suggest that virgin and memory T cells may differ fundamentally in their activation requirements, and suggest further that the accumulation, with age, of memory T cells accounts for the low responsiveness of old mice to non-cognate mitogens.
Flurkey
K
K
Department of Pathology, University of Michigan, Ann Arbor.
Stadecker
M
M
Miller
R A
RA
D000375:Aging; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000947:Antigens, Helminth / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism; D007156:Immunologic Memory; D007377:Interleukin-3 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000947:Antigens, Helminth; D004768:Enterotoxins; D006649:Histocompatibility Antigens; D007377:Interleukin-3; D016201:Receptors, Lymphocyte Homing; C031818:enterotoxin B, staphylococcal; D017493:Leukocyte Common Antigens