T cells in G1 provide a memory-like response to secondary stimulation.
The commitment of naive T cells to proliferate is a function of the strength and duration of stimuli mediated by the TCR and coreceptors. Ranges of 2-20 h of stimulation have been reported as necessary in vitro. Whether T cells actually experience uninterrupted stimulation for such long periods under physiological conditions is controversial. Here we ask whether commitment to proliferate requires continuous stimulation, or can T cells integrate intermittent periods of stimulation. T cells were stimulated for two short-term (subthreshold) periods (5-7 h) either sequentially or separated by an interval of rest. Naive lymph node T cells were able to integrate interrupted stimulation, even when the duration of rest was as long as 2 days. Furthermore, when short-term-stimulated T cells were separated by density, three populations were observed: low density blasts, intermediate density G(1) cells, and high density G(0) cells. Low density cells progressed to division without further stimulation, whereas G(0) and G(1) cells remained undivided. However, after a period of rest, a second subthreshold stimulation caused the G(1) but not the G(0) fraction to quickly proceed through the cell cycle. We conclude that noncycling T cells in the G(1) phase of the cell cycle remain in a state of readiness for prolonged periods of time, and may represent a population of memory-like effectors capable of responding rapidly to antigenic challenge.
Munitic
Ivana
I
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ryan
Philip E
PE
Ashwell
Jonathan D
JD
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000276:immunology; D049109:Cell Proliferation; D016193:G1 Phase / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015415:Biomarkers; D007376:Interleukin-2