An adoptive transfer system was used to monitor physically the behavio
r of a trace population of TCR transgenic T cells in vivo. After subcu
taneous injection of antigen in adjuvant, the antigen-specific cells a
ccumulated first in the paracortical region of the draining lymph node
s, proliferated there for several days, and then moved into lymph node
follicles, where they accounted for most of the T cells. They then di
sappeared slowly from the draining nodes, and the remaining cells were
hypersensitive to antigenic stimulation in vitro. In contrast, when t
he antigen was introduced into the blood, the antigen-specific cells r
apidly accumulated in the paracortical regions of all lymph nodes, pro
liferated there for a short time, but never entered follicles. Most of
the cells then rapidly disappeared, leaving behind a population that
was hyporesponsive to antigenic stimulation. These results provide a p
hysical basis for the classical finding that antigen-specific memory a
nd tolerance can be influenced by the form of antigen administration.