Separate roles for antigen recognition and lymph node inflammation in CD8+ memory T cell formation.
Priming of naive CD8(+) T cells by pathogens or vaccines generally involves their interaction with Ag-loaded dendritic cells (DCs) in the context of an inflamed lymph node. Lymph node activation fosters DC and T cell encounters and subsequently provides newly primed T cells with nurturing conditions. We dissected these two aspects by infusing in vitro primed CD8(+) T cells into naive recipient mice harboring a single activated lymph node and comparing the fate of these T cells with those infused into control recipients. Brief (20 h) in vitro priming empowered the T cells to expand in vivo without further Ag stimulation. This primary response was not affected by the presence or absence of a nonspecifically activated lymph node. In contrast, in vivo antigenic challenge after contraction of the primary response resulted in significantly stronger secondary T cell responses in mice harboring activated lymph nodes, demonstrating that the availability of an activated lymph node supported the generation of T cell memory in an Ag-unrelated manner. The presence of an activated lymph node during the expansion and contraction phase of the primary response did not endow T cells with an instructional program for increased survival or secondary expansion, but primarily served to conserve increased numbers of T cells.
Fransen
Marieke F
MF
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. M.F.Herbert-Fransen@lumc.nl
van Stipdonk
Marianne J
MJ
Sluijter
Marjolein
M
Schoenberger
Stephen P
SP
Melief
Cornelis J
CJ
Offringa
Rienk
R
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism
C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin