title: Stimulation of murine T cell subsets with anti-CD3 antibody. Age-related defects in the expression of early activation molecules.
abstract: Splenocytes from young (3 to 4 mo) and aged (24 to 26 mo) C57BL/6 mice were stimulated with anti-CD3 epsilon mAb in vitro. At the time of peak DNA synthesis (day 2), cells from aged mice incorporated congruent to 60% less [3H]TdR than cells from young mice. This age-related defect was not attributable to gross differences in anti-CD3 does optima, response kinetics, accessory cell function, numbers of T cells cultured, CD4+:CD8+ cell ratios or surface levels of CD3 epsilon molecules. In an attempt to analyze pre-S phase events in these responses, we monitored CD4+ and CD8+ cells in splenocyte cultures for the time-dependent expression of three T cell activation markers: RL388 Ag and IL-2R and transferrin R. Parallel analyses of mean T cell size and cell cycle phase distributions were performed. Non-activated T cells from both age groups similarly expressed moderate levels of RL388 Ag, low levels of transferrin R, and undetectable levels of IL-2R. Analysis of stimulated T cells revealed, in both age groups: 1) detectable increases in expression of all three markers by 6 h of culture, and continued increases associated with blastogenesis and G1 phase transit and 2) a preferential stimulation of the CD8+ subset to a state of high level marker expression. Age group comparisons of activation marker expression over time suggested that the age-related defect reflects proportionally smaller fractions of CD4+ and CD8+ cells that respond normally, rather than a general defect in all T cells or a subset-specific defect. Finally, we found that supernatants from aged donor cell cultures stimulated with anti-CD3 contained less Il-2 than those of young controls. Addition of an IL-2 containing supernatant to aged donor cell cultures increased, but did not restore, the S phase response on day 2; however, the response on day 3 was comparable to the peak (day 2) response of young controls. These data suggest that exogenous IL-2 can improve the aged response, perhaps by expanding the fraction of normally reactive T cells.
authors.affiliation: Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
authors.forename: D N
authors.initials: DN
authors.lastname: Ernst
authors.forename: W O
authors.initials: WO
authors.lastname: Weigle
authors.forename: D N
authors.initials: DN
authors.lastname: McQuitty
authors.forename: A L
authors.initials: AL
authors.lastname: Rothermel
authors.forename: M V
authors.initials: MV
authors.lastname: Hobbs
mesh_terms: D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000276:immunology*; D017252:CD3 Complex; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004247:DNA; D007376:Interleukin-2; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens