Long-term commitment to inflammation-seeking homing in CD4+ effector cells

Access of T effector cells to sites of inflammation is a prerequisite for an efficient action in immune defense and is mediated by different, partly tissue-specific sets of adhesion molecules. To what extent lymphocytes memorize the site of initial priming and develop organ-specific homing properties is still a matter of debate. Notably, data on the stability of homing receptor expression on T cells in vivo are largely lacking. We approached this question by the adoptive transfer of CD4(+) T cells sorted for the expression of P-selectin ligands, which contribute to migration into inflamed sites in skin and other tissues. We observed long-term expression of P-selectin ligands on roughly one-third of effector cells. On those cells that had lost P-selectin ligands, re-expression upon Ag challenge was observed but only within pLNs, similar to the organ-selective induction upon the primary activation of naive T cells. The frequency of cells stably expressing P-selectin ligands was higher when cells were repeatedly stimulated under permissive conditions in the presence of IL-12, indicating a gradual fixation of this phenotype. In line with that finding, isolated P-selectin ligand positive memory T cells showed the highest frequency of long-term expressing cells. A tissue-specific environment was not required for the long-term maintenance of P-selectin ligand expression on the subfraction of effector cells. These data indicate that the expression of selectin ligands can become clonally imprinted under certain conditions, but also that a major fraction of the cells remains flexible and subject to environmental modulation upon restimulation.