CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes

• Published in: The Journal of experimental medicine Vol. 199; no. 8; pp. 1113 - 1120
• Main Authors: Scimone, M Lucila, Felbinger, Thomas W, Mazo, Irina B, Stein, Jens V, Von Andrian, Ulrich H, Weninger, Wolfgang
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 19.04.2004
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - physiology; Cell Movement - drug effects; Chemokine CXCL12; Chemokines, CXC - physiology; Immunologic Memory; Lymph Nodes - cytology; Lymph Nodes - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Pertussis Toxin - pharmacology; Receptors, CCR7; Receptors, Chemokine - physiology; Receptors, Lymphocyte Homing - physiology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - physiology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20031645

Central memory CD8(+) T cells (T(CM)) confer superior protective immunity against infections compared with other T cell subsets. T(CM) recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that T(CM), unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that T(CM) migrate to PLNs at approximately 20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8(+) T cells in plt/plt PLNs displayed a T(CM) phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that T(CM) rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of T(CM) in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1alpha). Anti-CXCL12 also reduced homing of T(CM) to PLNs in WT animals by 20%, indicating a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from T(CM), whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.