Increased Apoptosis of T Cell Subsets in Aging Humans: Altered Expression of Fas (CD95), Fas Ligand, Bcl-2, and Bax

• Published in: The Journal of immunology (1950) Vol. 160; no. 4; pp. 1627 - 1637
• Main Authors: Aggarwal, Sudeepta, Gupta, Sudhir
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.1998
• Subjects: Adult; Aged; Aged, 80 and over; Aging - immunology; Antibodies, Monoclonal - pharmacology; Apoptosis - immunology; bcl-2-Associated X Protein; Fas Ligand Protein; fas Receptor - biosynthesis; fas Receptor - immunology; Female; Humans; Immunity, Innate; Ligands; Male; Membrane Glycoproteins - biosynthesis; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - physiology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.160.4.1627

Aging is associated with lymphopenia and progressive decline in T cell functions; however, the mechanisms underlying these defects are unclear. We analyzed the expression of genes promoting apoptosis (fas/fasL1 and bax) and those inhibiting apoptosis (bcl-2 and bcl-xL) in lymphocytes from aging and young subjects at the protein level, using flow cytometry/Western blotting, and at the mRNA level, using quantitative PCR. Susceptibility of T cell subsets to undergo anti-Fas-induced apoptosis was analyzed by propidium iodide staining, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, DNA fragmentation assay, and staining with Hoechst 33342 dye. An increased expression of Fas and Fas ligand and a decreased expression of Bcl-2 were observed in both CD4+ and CD8+ T cells from aging as compared with young controls. Increased Fas and decreased Bcl-2 expression were also found in memory cells of both CD4+ and CD8+ T cell subsets from aging. Bax expression was increased in lymphocytes from aging at both the protein and mRNA level. No significant difference was observed in Bcl-xL expression between aging and young; however, the ratio of Bax:Bcl-xL was increased in aging. An increased proportion of CD4+ and CD8+ T cell subsets from aging underwent apoptosis following anti-Fas Ab treatment as compared with CD4+ and CD8+ T cell subsets from young controls. These data suggest that increased apoptosis may be one of the mechanisms responsible for lymphopenia and T cell deficiency associated with human aging.