Age-related loss of immunoregulatory function in peripheral blood CD8 T cells

CD8+ T cells from young individuals become inhibitory for the (Staphylococcus aureus + interleukin 2)-induced differentiation of autologous B cells into immunoglobulin secreting cells (ISC) after exposure to pokeweed mitogen (PWM), dimaprit or intracellular cAMP raising agents, such as forskolin or dibutyryl-cAMP. In the present study this immunoregulatory activity was found to be lacking in CD8+ T cells from peripheral blood lymphocytes (PBL) of aged (> 67 years old) subjects. Splenic CD8+ T cells from most individuals examined, including some aged subjects, exhibited this activity. While an age-related decrease in the CD8+ T cell subset, primarily in the virgin CD8+ T cells in PBL, was detected, this decrease was not sufficient to explain a total absence of activity. There was no age-related decrease in cAMP upregulation by forskolin or dimaprit in peripheral blood T cells. However, whereas PWM induced a highly significant increase in mRNA for transforming growth factor-beta (TGF-beta) in T cells from young individuals, no such increase could be detected in T cells from aged subjects. It is suggested that the decrease in immunoregulatory activity in PBL from the elderly may at least in part be due to a decrease in TGF-beta production.