Proliferating CD4+ T cells undergo immediate growth arrest upon cessation of TCR signaling in vivo.
To investigate the role of TCR signaling in the exit of CD4+ T cells from cell cycle, we took advantage of a low frequency TEa T cell adoptive transfer technique as well as the Y-Ae mAb to interrupt Ag/MHC recognition before the completion of clonal expansion. Termination of TCR signaling after 36 h of Ag exposure caused an immediate reduction in cell size and deceleration of G1->SG2M phase cell cycle progression. As a consequence, clonal expansion in the absence of durable TCR signaling decreased by two-thirds. Thus, CD4+ T cells scan for the presence Ag throughout their clonal expansion response, and continuously adjust their rate of cell growth and G1->S phase transition to match their intensity of TCR signaling.
Yarke
Cory A
CA
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Dalheimer
Stacy L
SL
Zhang
Na
N
Catron
Drew M
DM
Jenkins
Marc K
MK
Mueller
Daniel L
DL
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D002455:Cell Division; D049109:Cell Proliferation; D008024:Ligands; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell