Aged T cells are hyporesponsive to costimulation mediated by CD28.
The ability of T cells to proliferate in response to a number of stimuli is impaired in healthy, aged individuals. T cells from young (2 to 4 mo) and aged (20 to 26 mo) mice were stimulated with immobilized anti-CD3 epsilon-chain mAb and soluble anti-CD28 mAb. T cells from young and aged mice proliferated comparably in response to anti-CD3 epsilon mAb alone. However, aged T cells were significantly less responsive to costimulation by anti-CD28 mAb. This decreased response of aged T cells was seen at all dosages tested of anti-CD3 epsilon and anti-CD28 mAbs and in the presence and absence of APC. Similar results were observed when costimulation was provided by B7-transfected L cell fibroblasts. T cells from young and aged mice had comparable expression of CD28 by flow cytometry, both before and after stimulation. The defect in response to CD28 was seen both in CD4+ and CD8+ T cells and in CD44lo (naive) and CD44hi (memory) T cells. The impaired response to costimulation mediated by CD28 on T cells from aged mice may be an important factor in reduced T cell responses associated with aging.
Engwerda
C R
CR
Department of Medicine, University of Maryland at Baltimore 21201.
Handwerger
B S
BS
Fox
B S
BS
D000375:Aging; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D018960:Hyaluronan Receptors; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011956:Receptors, Cell Surface / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing