Traffic of L-selectin-negative T cells to sites of inflammation

T cells responding to antigen in vivo down-regulate L-selectin, the lymph n ode homing receptor, as they develop into activated effector cells. The con comitant up-regulation of the proinflammatory adhesion molecules LFA-I, CD4 4, and VLA-4 suggests that, after their release into the circulation, they traffic to sites of antigen deposition and inflammation. Previous evidence, however, has suggested a role for L-selectin in the recruitment of both ne utrophils and lymphocytes into sites of inflammation, which would indicate that these L-selectin(-) effector cells could not be the precursors of infl ammatory cells. We therefore directly tested whether L-selectin(-) T cells activated in vivo are capable of homing to model inflammatory sites. L-sele ctin(-) cells isolated from mice primed with alloantigen or with a contact sensitizer migrated to inflammation markedly better than L-selectin(+) cell s from the same animals. Furthermore, the analogous population of CD44(hi)i ntegrin(hi) cells from intravenously primed L-selectin knockout mice traffi c efficiently to inflammatory sites and reject allogeneic skin grafts with normal kinetics. These data demonstrate that the previously described L-sel ectin(-) population of T cells that differentiate into effecters in spleen and lymph nodes subsequently traffic to inflammatory sites, due in part to their increased expression of other proinflammatory adhesion molecules.