Item Details

abstract

Immune function decreases with age. Most aspects of the immune system are affected but previously published data suggest dendritic cells (DC) largely escape this phenomenon. DC have three main functions: upregulation of cell surface expression of costimulatory molecules, antigen presentation, and cytokine secretion which lead to activation of T cells. The milieu of secreted cytokines determines the differentiation of activated naïve T helper (Th) cells into Th1, Th2, Th17 or T regulatory (Treg) cells. We show that bone marrow-derived DC (BMDC) differentiated from old male mice stimulated with Toll-like receptor (TLR) agonists, alone or in combination, secrete increased IL-23, a cytokine involved in the Th17 cytokine axis. IL-12, a cytokine involved in the Th1 axis does not change. This shift in cytokine secretion occurs between 6 and 12 months of age and is evident after stimulation with several TLR agonists, but most prominently with the combination of the TLR 4 and TLR 7/8 agonists, lipopolysaccharide (LPS) and R848, respectively. The superiority of this combination in stimulating cytokine secretion by BMDC from aged mice led us to investigate its effect on Th differentiation. BMDC stimulated with the combination of LPS/R848 triggered the differentiation of Th1 cells. This was true regardless of the age of the mouse from which the BMDC or the T cells were isolated. However, the addition of exogenous IL-23 to these DC/T cell cultures blunted Th1 differentiation suggesting IL-23 might play a role in immune senescence. We conclude that BMDC from aged mice are capable of triggering robust Th1 differentiation when stimulated with the proper TLR agonists. The retention of function by DC with age may provide strategies to be exploited in the formulation of new vaccines with enhanced efficacy in the elderly.

subject

Dendritic Cells

Aging

T Helper Cells

contributor

Myer, Rebecca (author)

Elizabeth M. Hiltbold (committee chair)

Kevin P. High (committee member)

Michael C. Seeds (committee member)

Charles E. McCall (committee member)

Nammalwar Sriranganathan (committee member)

date

2009-03-19T14:15:40Z (accessioned)

2010-06-18T18:58:17Z (accessioned)

2009-03-19T14:15:40Z (available)

2010-06-18T18:58:17Z (available)

2009-03-19T14:15:40Z (issued)

degree

Molecular Medicine (discipline)

identifier

http://hdl.handle.net/10339/14749 (uri)

language

en_US (iso)

publisher

Wake Forest University

rights

Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)

title

Aging Dendritic Cell Function and Effects on T Helper Cell Differentiation

type

Dissertation