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 predominately 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.