This study examined long-term phenotypic and functional effects of TCR
ligation in vivo. Flow cytometric analysis of T cells from mice treat
ed with anti-CD3 revealed an increase in CD44 expression in both the C
D4(+) and CD8(+) populations. The phenotypic changes were a result of
TCR engagement, because treatment with staphylococcal enterotoxin B (S
EB) resulted in a preferential increase in CD44 expression on the SEB-
reactive V beta 8 T cells. In addition, the percentage of cells expres
sing Ly-6C increased among the CD8(+) subset after anti-CD3 treatment
and in the V beta 8(+) CD8(+) subset after treatment with SEB. Finally
, the TCR transgenic (Tg) mouse strain 2C was used to confirm that the
phenotypic changes can be induced by exposure to a physiologic ligand
(H-2L(d)). Before treatment, nearly all of the Tg(+)CD8(+) cells were
CD44(low)/Ly-6C(-). Tg(+) peritoneal exudate T cells isolated from mi
ce challenged with P815 cells (H-2L(d)) up-regulated Ly-6C and secrete
d higher levels of IFN-gamma on a per Tg(+) CD8(+) T cell basis after
treatment. Taken together, these data indicate that in vivo TCR/CD3 en
gagement results in phenotypic and functional changes in T cells. Furt
hermore, Ly-6C expression correlates with an increase in IFN-gamma pro
duction after antigenic stimulation of CD8(+) T cells, suggesting that
it is a ''memory'' marker that correlates with Ag-specific functional
changes in CD8(+) T cells.