Age-related changes in lymphocytes are most prominent in the T cell compartment. 
There have been substantial numbers of reports on T cell function in aged mice 
and humans, such as on the production of Th1 and Th2 cytokines, but the results 
show considerable variation and contradictions. In the present study, we used 8- 
to 12-mo-old aging mice and a well-established in vitro Th1/Th2 cell 
differentiation culture system to identify molecular defects in Th1/Th2 cell 
differentiation that can be detected in the relatively early stages of aging. 
The capability to differentiate into Th2 cells is reduced in aging mouse CD4(+) 
T cells. Decreased activation of the ERK MAPK cascade upon TCR stimulation, but 
normal intracellular-free calcium ion concentration mobilization and normal 
IL-4-induced STAT6 activation were observed in aging mouse CD4(+) T cells. In 
addition, reduced expression of GATA3 was detected in developing Th2 cells. 
Chromatin remodeling of the Th2 cytokine gene locus was found to be impaired. 
Th2-dependent allergic airway inflammation was milder in aging mice compared 
with in young adult mice. These results suggest that the levels of Th2 cell 
differentiation and resulting Th2-dependent immune responses, including allergic 
airway inflammation, decline during aging through defects in the activation of 
the ERK MAPK cascade, expression of GATA3 protein and GATA3-dependent chromatin 
remodeling of the Th2 cytokine gene locus. In the present study, we provide the 
first evidence indicating that a chromatin-remodeling event in T cells is 
impaired by aging.