Alterations in cyclic nucleotides and cyclase-specific activities in T lymphocytes of aging normal humans and patients with Down's syndrome.
The levels of cyclic adenosine 3'5'-monophosphate (cAMP) in unstimulated (resting) peripheral blood thymus-derived lymphocytes (T cells) from normal old humans and young-adult Down's syndrome (DS) patients were markedly decreased when compared with those of young normal humans. By contrast, the cyclic guanosine 3'5'-monophosphate (cGMP) in resting T cells from normal old and young-adult DS patients were greatly increased. The cAMP/cGMP ratios for unstimulated T cells therefore declined in normal aged and DS subjects. The specific activity of adenylate cyclase (ATP pyrophosphate-lyase[cycling]E.C.4.6.1.1) was elevated in T cells from the aged and DS groups, whereas that of guanylate cyclase (GTP pyrophosphate-lyase[cycling]E.C.4.6.1.2) decreased with age and in DS. These results denote the existence of substantial age-related biochemical changes in peripheral T cells. An imbalance in resting cyclic nucleotide levels and their generating enzymes in T cells of normal aging and DS subjects might contribute to the immune dysfunction occurring both with aging and in DS.
D000262:Adenylyl Cyclases / Q000097:blood*; D000328:Adult; D000368:Aged; D000375:Aging; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D004314:Down Syndrome / Q000276:immunology; D005260:Female; D006162:Guanylate Cyclase / Q000097:blood*; D006801:Humans; D008297:Male; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP