Dynamic programming of CD8+ T cell trafficking after live viral immunization.
After viral infection, activated T cells are present in multiple tissues regardless of the infection route. How these cells acquire pleiotropic homing ability is unclear. By using a cutaneous vaccinia virus infection model, we demonstrate that regulation of T cell trafficking is multiphasic. Upon completion of three cell divisions, CD8+ T cells upregulated specific skin-homing molecules within draining lymph nodes (LN). By 60 hr after infection, some activated T cells reached the infected tissue, while others entered distant antigen-free LN. These latter cells continued to divide and acquire additional tissue-homing molecules in this new setting, independent of antigen presentation. After viral clearance, the initial skin-homing imprint became the predominant homing phenotype on memory cells and provided superior protection against secondary cutaneous challenge. These observations demonstrate a mechanism by which T cells provide both immediate tissue-specific immune control at the pathogen entry site and a more flexible systemic protection against pathogen dissemination.
Liu
Luzheng
L
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. lzliu@rics.bwh.harvard.edu
Fuhlbrigge
Robert C
RC
Karibian
Kara
K
Tian
Tian
T
Kupper
Thomas S
TS
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000956:Antigens, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines