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 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.
Scimone
M Lucila
ML
The CBR Institute for Biomedical Research, 200 Longwood Ave., Boston, MA 02115, USA.
Felbinger
Thomas W
TW
Mazo
Irina B
IB
Stein
Jens V
JV
Von Andrian
Ulrich H
UH
Weninger
Wolfgang
W
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D037342:Pertussis Toxin / Q000494:pharmacology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology
C515371:Ccr7 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D037342:Pertussis Toxin