Age-related changes in the activation requirements of human CD4+ T-cell subsets.
In agreement with previous studies, we found that the proliferative response of unfractionated T-cells to phytohaemagglutinin (PHA) was severely impaired in healthy aged individuals (70-85 years). On the other hand, we did not observe significant differences between aged and young adults in T-cell responsiveness to mab OKT3 (anti-CD3). PHA responses in "old" T-cells could be substantially improved, however, by the addition of recombinant interleukin-2 (rIL-2) or KOLT2 (anti-CD28 mab). When individual CD4+ T-cell subpopulations were isolated from young and old donors and stimulated with PHA in the presence of autologous accessory cells, age-related deficiencies were seen in both CD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) cell populations. Further analysis using a panel of coactivators in cultures depleted of accessory cells identified specific abnormalities in the CD2 or alternate pathway of T-cell activation. These were predominantly seen in CD4+ naive T-cells. The capacity of rIL-2, KOLT2, and PMA to restore, at least partially, T-cell responsiveness in the aged suggests a defect(s) in an early signal transduction mechanism.
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park 5042, Australia.
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Beckman
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Dimopoulos
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Xu
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Ahern
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Bradley
D000328:Adult; D000367:Age Factors; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D018801:CD2 Antigens; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology; D011994:Recombinant Proteins
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens