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The CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, MA 02115

Address correspondence to Ulrich H. von Andrian, The CBR Institute for Biomedical Research, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 278-3130; Fax: (617) 278-3190; email: uva{at}cbr.med.harvard.edu

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 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-1). 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.

Key Words: lymphocytes • chemokines • migration • secondary lymphoid organs • recirculation

The present address of J.V. Stein is National Center for Biotechnology, CNB/CSIC, 28049 Madrid, Spain.

The present address of W. Weninger is The Wistar Institute, Philadelphia, PA 19104.

Abbreviations used in this paper: GFP, green fluorescent protein; GPCR, G_i-protein coupled receptor; HEV, high endothelial venule; IVM, intravital microscopy; MLN, mesenteric LN; PLN, peripheral LN; plt, paucity of lymph node T cells; PTX, pertussis toxin; T_CM, central memory T cells; T_EM, effector memory T cells; TRITC, tetramethylrhodamine-5-isothiocyanate.

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