Antigen availability determines CD8⁺ T cell-dendritic cell interaction kinetics and memory fate decisions.
T cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8⁺ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics.
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Sarah E
SE
Henrickson
Mario
M
Perro
Scott M
SM
Loughhead
Balimkiz
B
Senman
Susanne
S
Stutte
Michael
M
Quigley
Gabriela
G
Alexe
Matteo
M
Iannacone
Michael P
MP
Flynn
Shaida
S
Omid
Jonathan L
JL
Jesneck
Sabrina
S
Imam
Thorsten R
TR
Mempel
Irina B
IB
Mazo
W Nicholas
WN
Haining
Ulrich H
UH
von Andrian
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059467:Transcriptome / Q000276:immunology