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.
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, NY 10016, USA.
G M
GM
Crisi
L Z
LZ
Chen
C
C
Huang
G J
GJ
Thorbecke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D000242:Cyclic AMP / Q000302:isolation & purification; D017259:Dimaprit / Q000494:pharmacology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D008297:Male; D011043:Pokeweed Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics
D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000242:Cyclic AMP; D017259:Dimaprit