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.
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 alpha-GalCer stimulation using either the Valpha24/Vbeta11 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.
Jing
Yu
Y
Department of Internal Medicine, The Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, 2126 Lewis Hall, Norfolk, VA 23507, USA.
Gravenstein
Stefan
S
Chaganty
N Rao
NR
Chen
Nianyong
N
Lyerly
Kim Herbert
KH
Joyce
Sebastian
S
Deng
Yuping
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D018418:Th2 Cells / Q000145:classification / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide