Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood

• Published in: Experimental gerontology 2007-08, Vol.42 (8), p.719-732
• Main Authors: Jing, Yu, Gravenstein, Stefan, Rao Chaganty, N., Chen, Nianyong, Lyerly, Kim Herbert, Joyce, Sebastian, Deng, Yuping
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aging; Aging - immunology; Antigens, CD1 - metabolism; Antigens, CD1d; Cytokines; Cytokines - biosynthesis; Female; Galactosylceramides - immunology; Humans; Immune senescence; In Vitro Techniques; Killer Cells, Natural - classification; Killer Cells, Natural - immunology; Lymphocyte Activation; Male; Middle Aged; NKT cells; Receptors, Antigen, T-Cell - metabolism; T-Lymphocyte Subsets - classification; T-Lymphocyte Subsets - immunology; Th1/Th2; Th2 Cells - classification; Th2 Cells - immunology
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2007.01.009

NKT cells are important for initiating and regulating immune responses. We investigated the age-related changes in the CD1d-restricted semi-invariant NKT (iNKT) cells in peripheral blood of healthy adults. The iNKT cell frequency was 2.5- to 10.7-fold less in healthy elderly subjects (61 years and over) compared to the healthy young subjects (20–40 years, p < 0.001). This age-related decline in iNKT cells was observed both in freshly isolated PBMC and in cultures where iNKT cells were enriched by α-GalCer stimulation using either the Vα24/Vβ11 TCR antibody pair or the CD1d-tetramer as the iNKT cell marker. The decline in frequency was associated with an alteration in the iNKT cell subset compositions: an increase in the proportion of CD4 + subset and a decrease in the proportion of CD4/CD8 double-negative (DN) subset. The age-related decline in iNKT cells and changes in subset composition were independent from the age-related changes of conventional T cells/T cell subsets. Additionally, there was a Th1 to Th2 shift in the cytokine response profile from iNKT cells with aging. We conclude that aging is associated with a significant decline in iNKT cell frequency in peripheral blood, accompanied with alterations in subset composition and cytokine response profile.