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

Central memory CD8(+) T cells (T-CM) confer superior protective immunity against infectious 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 riot express CCR7 ligands in secondary lymphoid organs, revealed that T-CM migrate to PLNs at similar to20% 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 hatter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.