Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression.
The decline in adaptive immunity, naïve T-cell output and a contraction in the peripheral T cell receptor (TCR) repertoire with age are largely attributable to thymic involution and the loss of critical cytokines and hormones within the thymic microenvironment. To assess the molecular changes associated with this loss of thymic function, we used cDNA microarray analyses to examine the transcriptomes of thymocytes from mice of various ages ranging from very young (1 month) to very old (24 months). Genes associated with various biological and molecular processes including oxidative phosphorylation, T- and B- cell receptor signaling and antigen presentation were observed to significantly change with thymocyte age. These include several immunoglobulin chains, chemokine and ribosomal proteins, annexin A2, vav 1 and several S100 signaling proteins. The increased expression of immunoglobulin genes in aged thymocytes could be attributed to the thymic B cells which were found to be actively producing IgG and IgM antibodies. Upon further examination, we found that purified thymic T cells derived from aged but not young thymi also exhibited IgM on their cell surface suggesting the possible presence of auto-antibodies on the surface thymocytes with advancing age. These studies provide valuable insight into the cellular and molecular mechanisms associated with thymic aging.
Lustig
Ana
A
Laboratory of Immunology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Carter
Arnell
A
Bertak
Dorothy
D
Enika
Divya
D
Vandanmagsar
Bolormaa
B
Wood
William
W
Becker
Kevin G
KG
Weeraratna
Ashani T
AT
Taub
Dennis D
DD
D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D020407:Internet; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D011687:Purines / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics
D001323:Autoantibodies; D007075:Immunoglobulin M; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011687:Purines; D014451:Ubiquinone