T cell and APC dynamics in situ control the outcome of vaccination.
The factors controlling the progression of an immune response to generation of protective memory are poorly understood. We compared the in situ and ex vivo characteristics of CD8 T cells responding to different forms of the same immunogen. Immunization with live Listeria monocytogenes, irradiated L. monocytogenes (IRL), or heat-killed L. monocytogenes (HKL) induced rapid activation of CD8 T cells. However, only IRL and live L. monocytogenes inoculation induced sustained proliferation and supported memory development. Gene and protein expression analysis revealed that the three forms of immunization led to three distinct transcriptional and translational programs. Prior to cell division, CD8 T cell-dendritic cell clusters formed in the spleen after live L. monocytogenes and IRL but not after HKL immunization. Furthermore, HKL immunization induced rapid remodeling of splenic architecture, including loss of marginal zone macrophages, which resulted in impaired bacterial clearance. These results identify initial characteristics of a protective T cell response that have implications for the development of more effective vaccination strategies.
Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030, USA.
Kamal M
KM
Khanna
David A
DA
Blair
Anthony T
AT
Vella
Stephen J
SJ
McSorley
Sandip K
SK
Datta
Leo
L
Lefrançois
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D007115:Immunization Schedule; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic