Abstract
We isolated highly purified CD8+CD28+ and CD8+CD28− T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28− T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8+CD28− (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28− T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types.
Similar content being viewed by others
References
Alexandrakis MG et al (2003) Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma. Ann Hematol 82(1):19–23
Alonso MA, Weissman SM (1987) cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. Proc Natl Acad Sci USA 84(7):1997–2001. doi:10.1073/pnas.84.7.1997
Day CL et al (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443(7109):350–354. doi:10.1038/nature05115
Eisen MB et al (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95(25):14863–14868. doi:10.1073/pnas.95.25.14863
Fagnoni FF et al (1996) Expansion of cytotoxic CD8+ CD28− T cells in healthy ageing people, including centenarians. Immunology 88(4):501–507. doi:10.1046/j.1365-2567.1996.d01-689.x
Fann M et al (2005) Gene expression characteristics of CD28null memory phenotype CD8+ T cells and its implication in T-cell aging. Immunol Rev 205:190–206. doi:10.1111/j.0105-2896.2005.00262.x
Fitzgerald JE et al (1995) Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol 154(7):3538–3547
George AJ, Ritter MA (1996) Thymic involution with ageing: obsolescence or good housekeeping? Immunol Today 17(6):267–272. doi:10.1016/0167-5699(96)80543-3
Hiraide A et al (2005) Fas polymorphisms influence susceptibility to autoimmune hepatitis. Am J Gastroenterol 100(6):1322–1329. doi:10.1111/j.1572-0241.2005.41053.x
Holub MC et al (2002) Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells. Immunol Lett 82(1–2):79–84. doi:10.1016/S0165-2478(02)00022-6
Hou M et al (2004) Antisense Tiam1 down-regulates the invasiveness of 95D cells in vitro. Acta Biochim Biophys Sin (Shanghai) 36(8):537–540
Kaneko H et al (1996) Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis. Clin Exp Immunol 106(2):218–229. doi:10.1046/j.1365-2249.1996.d01-849.x
Mi H et al (2005) The PANTHER database of protein families, subfamilies, functions and pathways. Nucleic Acids Res 33(Database issue):D284–D288. doi:10.1093/nar/gki078
Nociari MM, Telford W, Russo C (1999) Postthymic development of CD28−CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype. J Immunol 162(6):3327–3335
Okkenhaug K, Vanhaesebroeck B (2003) PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 3(4):317–330. doi:10.1038/nri1056
Pavlidis P, Noble WS (2001) Analysis of strain and regional variation in gene expression in mouse brain. Genome Biol 2(10):RESEARCH0042
Pfister G et al (2006) Naive T cells in the elderly: are they still there? Ann N Y Acad Sci 1067:152–157. doi:10.1196/annals.1354.018
Posnett DN et al (1994) Clonal populations of T cells in normal elderly humans: the T cell equivalent to “benign monoclonal gammapathy”. J Exp Med 179(2):609–618. doi:10.1084/jem.179.2.609
Radfar S, Davrinche C, Hollande E (2005) Serial in vivo loss and in vitro gain of Fas expression and function in human cancerous pancreatic duct cells. Int J Cancer 115(2):214–223. doi:10.1002/ijc.20802
Rainer J et al (2006) CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis. Nucleic Acids Res 34(Web Server issue):W498–W503
Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386
Saeed AI et al (2003) TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34(2):374–378
Sallusto F et al (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401(6754):708–712. doi:10.1038/44385
Sansoni P et al (1997) T lymphocyte proliferative capability to defined stimuli and costimulatory CD28 pathway is not impaired in healthy centenarians. Mech Ageing Dev 96(1–3):127–136. doi:10.1016/S0047-6374(97)01887-3
Schwab R et al (1997) Expanded CD4+ and CD8+ T cell clones in elderly humans. J Immunol 158(9):4493–4499
Sperling AI, Bluestone JA (1996) The complexities of T-cell co-stimulation: CD28 and beyond. Immunol Rev 153:155–182. doi:10.1111/j.1600-065X.1996.tb00924.x
Stulnig T et al (1995) Reference intervals for human peripheral blood lymphocyte subpopulations from ‘healthy’ young and aged subjects. Int Arch Allergy Immunol 108(3):205–210
Tarazona R et al (2000) Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mech Ageing Dev 121(1–3):77–88. doi:10.1016/S0047-6374(00)00199-8
van Doorn R et al (2004) Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sezary syndrome identified by gene expression analysis. Cancer Res 64(16):5578–5586. doi:10.1158/0008-5472.CAN-04-1253
Wills MR et al (2002) Identification of naive or antigen-experienced human CD8(+) T cells by expression of costimulation and chemokine receptors: analysis of the human cytomegalovirus-specific CD8(+) T cell response. J Immunol 168(11):5455–5464
Acknowledgements
The authors thank Michael Keller and Brigitte Jenewein for collecting blood samples. This work was supported by the Austrian Science Fund (Projects S9308-B05 and S9309-B05
).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lazuardi, L., Herndler-Brandstetter, D., Brunner, S. et al. Microarray analysis reveals similarity between CD8+CD28− T cells from young and elderly persons, but not of CD8+CD28+ T cells. Biogerontology 10, 191–202 (2009). https://doi.org/10.1007/s10522-008-9167-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-008-9167-1