Maintenance of CCL5 mRNA stores by post-effector and memory CD8 T cells is dependent on transcription and is coupled to increased mRNA stability.
Immunological memory is associated with the display of improved effector functions by cells of the adaptive immune system. The storage of untranslated mRNA coding for the CCL5 chemokine by CD8 memory cells is a new process supporting the immediate display of an effector function. Here, we show that, after induction during the primary response, high CCL5 mRNA levels are specifically preserved in CD8 T cells. We have investigated the mechanisms involved in the long-term maintenance of CCL5 mRNA levels by memory CD8 T cells. We demonstrate that the CCL5 mRNA half-life is increased in memory CD8 T cells and that these cells constitutively transcribe ccl5 gene. By inhibiting ccl5 transcription using IL-4, we demonstrate the essential role of transcription in the maintenance of CCL5 mRNA stores. Finally, we show that these stores are spontaneously reconstituted when the inhibitory signal is removed, indicating that the transcription of ccl5 is a default feature of memory CD8 T cells imprinted in their genetic program.
Marçais
Antoine
A
INSERM, U503, Lyon, France.
Tomkowiak
Martine
M
Walzer
Thierry
T
Coupet
Charles-Antoine
CA
Ravel-Chapuis
Aymeric
A
Marvel
Jacqueline
J
D016475:3T3 Cells; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D007156:Immunologic Memory / Q000235:genetics*; D047468:Immunoprecipitation; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020871:RNA Stability; D023121:RNA, Messenger, Stored / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology*
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D023121:RNA, Messenger, Stored; D015847:Interleukin-4