Molecular dissection of T-cell differentiation defects in the old CD8 T cell (113.12)

• Published in: The Journal of immunology (1950) Vol. 186; no. 1_Supplement; pp. 113 - 113.12
• Main Authors: Renkema, Kristin, Rudd, Brian, Li, Gang, Samadder, Partha, Smithey, Megan, Nikolich-Zugich, Janko
• Format: Journal Article
• Language: English
• Published: 01.04.2011
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.113.12

Abstract One in eight people are 65 years and older in the United States; this population is expected to double within the next 50 years. Alarmingly, infectious diseases remain amongst the leading causes for death in people over 65 years old. Widespread defects in the immune system have been found to increase with age, including qualitative and quantitative decline with adaptive immunity. CD8 T cells have been found to decrease in both number and function in aged mice. We recently found that in response to systemic Listeria monocytogenes (Lm) infection, old mice mobilize fewer Lm-specific CD8 T cells. Moreover, these cells exhibited lower effector cytokine production, and are less polyfunctional. We evaluated the expression of key transcription factors crucial to effector CD8 T cell development in adult and old CD8 T cells in the mouse. We found that in response to in vivo stimulation, old CD8 T cells exhibited altered expression of T-homeobox transcription factors , correlating with lower expression of interferon-gamma (IFNγ), tumor necrosis factor alpha (TNFα) and granzyme B. Altered transcriptional activation may constitute a common denominator underlying suboptimal function of old CD8 T cells in response to primary infection. Experiments are in progress to correct these defects and improve function of aged CD8 T cells.