Rapid proliferation of activated lymph node CD4+ T cells is achieved by greatly curtailing the duration of gap phases in cell cycle progression

Abstract

Peripheral T cells are in G0 phase and do not proliferate. When they encounter an antigen, they enter the cell cycle and proliferate in order to initiate an active immune response. Here, we have determined the first two cell cycle times of a leading population of CD4 + T cells stimulated by PMA plus ionomycin in vitro. The first cell cycle began around 10 h after stimulation and took approximately 16 h. Surprisingly, the second cell cycle was extremely rapid and required only 6 h. T cells might have a unique regulatory mechanism to compensate for the shortage of the gap phases in cell cycle progression. This unique feature might be a basis for a quick immune response against pathogens, as it maximizes the rate of proliferation.

Rapid G0/1 transition and cell cycle progression in CD8+ T cells compared to CD4+ T cells following in vitro stimulation

“…From this analysis, we determined the minimum time that CD8 + T cells need to complete the first and second cell cycles and these were approximately 2 and 3 hr shorter than those of CD4 + T cells, respectively. These results suggest that CD8 + T cells are capable of driving each cell cycle in one hour less than the CD4 + T cells . This finding is consistent with the result of the proliferation rate determined using the mean division number described above (Fig.…”

“…We have studied G0/1 transition and the cell cycle progression of naive CD4 + T cells following stimulation with PMA plus ionomycin and anti‐CD28 mAb . Using the same approach, we further examined the difference between CD4 + and CD8 + T‐cell proliferation.…”

“…The cells in the gate presented in the dot plots are Pyronin Y positive. (B) The Pyronin Y‐positive population in CD8 + T cells (□) was determined at various time points by FACS as in CD4 + T cells (▪) and the average ± SEM from three independent experiments is plotted against time. (C,D) The population in CD8 + T cells that experienced cell division once () or twice () was determined at various time points by FACS as in CD4 + T cells (●, ) and the average ± SEM from three independent experiments is plotted against time.…”

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

“…First, memory T cells have a lower activation threshold and are less co-stimulation dependent [10]. Therefore, upon re-challenge, memory T cells will generate robust effector responses more effectively and faster as compared with a primary T cell response [11][12][13]. Similar to the effector response generated by recently-activated naive T cells, the effector response of memory T cells is dependent on the nature and context of their encounter with their cognate antigen, for example provided by cues such as cytokines in the microenvironment [14].…”

Macropinocytosis drives T cell growth by sustaining the activation of mTORC1

“…T cell macropinocytosis is necessary for G1 growth. T cells activated with CD3/28 mAb show major increases in cell size between 12 and 20 h post-stimulation, which corresponds to the G1 phase of the cell cycle 24 ( Supplementary Fig. 3a).…”