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* Experimentelle Rheumatologie, Medizinische Klinik, Charité and Deutsches Rheumaforschungszentrum, and
Molekulare Tumorgenetik und Immungenetik, Max Delbrück Centrum fur Molekulare Medizin, Berlin, Germany
Chemokines and their receptors fulfill specialized roles in
inflammation and under homeostatic conditions. CCR7 and its ligands,
CCL19 and CCL21, are involved in lymphocyte recirculation through
secondary lymphoid organs and additionally navigate lymphocytes into
distinct tissue compartments. The role of CCR7 in the migration of
polarized T effector/memory cell subsets in vivo is still poorly
understood. We therefore analyzed murine and human CD4+
cytokine-producing cells developed in vivo for their chemotactic
reactivity to CCR7 ligands. The responses of cells producing cytokines,
such as IFN-
, IL-4, and IL-10, as well as of subsets defined by
memory or activation markers were comparable to that of naive
CD4+ cells, with slightly lower reactivity in cells
expressing IL-10 or CD69. This indicates that CCR7 ligands are able to
attract naive as well as the vast majority of activated and
effector/memory T cell stages. Chemotactic reactivity of these cells
toward CCL21 was absent in CCR7-deficient cells, proving that effector
cells do not use alternative receptors for this chemokine. Th1 cells
generated from CCR7-/- mice failed to enter lymph nodes
and Peyer’s patches, but did enter a site of inflammation. These
findings indicate that CD4+ cells producing effector
cytokines upon stimulation retain the capacity to recirculate through
lymphoid tissues via CCR7.
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