CXCL12 Mediates CCR7-independent Homing of Central Memory Cells, But Not Naive T Cells, in Peripheral Lymph Nodes
Copyright policy )CXCL12 Mediates CCR7-independent Homing of Central Memory Cells, But Not Naive T Cells, in Peripheral Lymph Nodes
Central memory CD8+ T cells (TCM) confer superior protective immunity against infections compared with other T cell subsets. TCM recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that TCM, 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 TCM 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 TCM phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that TCM rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of TCM in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1α). Anti-CXCL12 also reduced homing of TCM 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 TCM, whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.
- Harvard University United States
- Biomedical Research Institute United States
Mice, Knockout, Mice, Inbred BALB C, Receptors, CCR7, Receptors, Lymphocyte Homing, Mice, Transgenic, CD8-Positive T-Lymphocytes, Article, Chemokine CXCL12, Mice, Mutant Strains, Mice, Inbred C57BL, Mice, Pertussis Toxin, Cell Movement, T-Lymphocyte Subsets, Animals, Receptors, Chemokine, Lymph Nodes, Chemokines, CXC, Immunologic Memory
Mice, Knockout, Mice, Inbred BALB C, Receptors, CCR7, Receptors, Lymphocyte Homing, Mice, Transgenic, CD8-Positive T-Lymphocytes, Article, Chemokine CXCL12, Mice, Mutant Strains, Mice, Inbred C57BL, Mice, Pertussis Toxin, Cell Movement, T-Lymphocyte Subsets, Animals, Receptors, Chemokine, Lymph Nodes, Chemokines, CXC, Immunologic Memory
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