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.