Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3.
Research into the age-associated decline in the immune system has focused on the factors that contribute to the accumulation of senescent CD8 T cells. Less attention has been paid to the non-immune factors that may maintain the pool of naïve CD8 T cells. Here, we analyzed the status of the naïve CD8 T-cell population in healthy nonagenarians (>or=90-year-old), old (60-79-year-old), and young (20-34-year-old) subjects. Naïve CD8 T cells were defined as CD28(+)CD95(-) as this phenotype showed a strong co-expression of the CD45RA(+), CD45RO(-), and CD127(+) phenotypes. Although there was an age-associated decline in the percentage of CD28(+)CD95(-) CD8 T cells, the healthy nonagenarians maintained a pool of naïve CD28(+)CD95(-) cells that contained T-cell receptor excision circles (TREC)(+) cells. The percentages of naïve CD28(+)CD95(-) CD8 T cells in the nonagenarians correlated with the sera levels of insulin-like growth factor binding protein 3 (IGFBP3) and leptin. Higher levels of triiodothyronine (T3) negatively correlated with the accumulation of TREC(-)CD28(-)CD95(+) CD8 T cells from nonagenarians. These results suggest a model in which IGFBP3, leptin and T3 act as non-immune factors to maintain a larger pool of naïve CD8 T cells in healthy nonagenarians.
Chen
Jian
J
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Li
Jun
J
Lim
Fei Chu
FC
Wu
Qi
Q
Douek
Daniel C
DC
Scott
Donald K
DK
Ravussin
Eric
E
Hsu
Hui-Chen
HC
Jazwinski
S Michal
SM
Mountz
John D
JD
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016922:Cellular Senescence / Q000276:immunology; D015331:Cohort Studies; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D020738:Leptin / Q000097:blood*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008145:Louisiana; D008875:Middle Aged; D014284:Triiodothyronine / Q000097:blood*; D015854:Up-Regulation; D055815:Young Adult; D019014:fas Receptor / Q000032:analysis
D018106:CD28 Antigens; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D053699:Interleukin-7 Receptor alpha Subunit; D020738:Leptin; D019014:fas Receptor; D014284:Triiodothyronine; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human