CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.
CCR7 is an important chemokine receptor that regulates T cell trafficking and compartmentalization within secondary lymphoid organs. However, the T cell-intrinsic role of CCR7 during infection in the spleen is not well understood. This study was designed to understand how CCR7-dependent localization and migration of CD8(+) T cells in different compartments of the spleen affected the primary and recall responses after infection. To this end, we used adoptive transfer of naive Ag-specific CD8 T cells (OT-I) that either lacked CCR7 or constitutively expressed CCR7 (CD2-CCR7) in mice that were subsequently infected i.v. with Listeria monocytogenes. We show that naive CCR7(-/-)CD8(+) T cells failed to enter the T cell zone, whereas CD2-CCR7 OT-I cells were exclusively confined to the T cell zones of the spleen. Surprisingly, however, CCR7(-/-) OT-I cells entered the T cell zones after infection, but the entry and egress migratory pattern of these cells was dysregulated and very distinct compared with wild-type OT-I cells. Moreover, CCR7-deficient OT-I cells failed to expand robustly when compared with wild-type OT-I cells and were preferentially skewed toward a short-lived effector cell differentiation pattern. Interestingly, CCR7(-/-), CD2-CCR7, and wild-type OT-I memory cells responded equally well to rechallenge infection. These results highlight a novel role of CCR7 in regulating effector CD8 T cell migration in the spleen and demonstrate differential requirement of CCR7 for primary and secondary CD8 T cell responses to infection.
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and.
Naveen
N
Sharma
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and.
Alexandre P
http://orcid.org/0000-0001-8746-2459
AP
Benechet
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and.
Leo
L
Lefrançois
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and Department of Pediatrics, University of Connecticut Health Center, Farmington, CT 06030 kkhanna@uchc.edu.
Kamal M
http://orcid.org/0000-0002-9328-3817
KM
Khanna
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7