Table 1.

Summary of observations from model simulations and data analysis.

Scenario		Model observation	Supporting evidence
High antigen dose	1	Differentiation into Th cells	(18)
	2	Transient FOXP3 expression	(69), This paper)
	3	pS6 high	(18, 27)
	4	IL-2 increases early after stimulation and remains high	(64)
Low antigen dose	5	Differentiation into Treg cells	(17, 18, 22)
	6	Transient IL2 expression	Prediction,
	7	pS6 low	(18, 27)
	8	Delayed FOXP3 expression (compared with HD)	Prediction
High antigen dose + TGFβ	9	Differentiation into Treg cells	(15, 20, 27)
	10	pS6 high, Foxp3+	(This paper)
	11	Foxp3 increases very early, before pS6	Prediction
	12	Unstable Treg phenotype – TGFβ removal switches cells back to Th phenotype	(70)
High antigen dose + inhibitor addition	13	NFAT inhibition still results in Th phenotype	(27)
	14	NFAT inhibition leads to several different phenotypes (Th and inactive)	Prediction
	15	mTORC1/Akt inhibition induces Treg phenotype	(27, 30)
High antigen dose + antigen removal	16	Mixed population of Treg, Th and inactivated cells	(27)
	17	11 different phenotypes observed	Prediction
	18	Treg cell population size changes with removal time (never 100%)	Prediction, (27)
	19	Th cell population size increases slowly to 100% with increasing removal time	Prediction
	20	Feedback between PTEN and Foxp3 critical for stable Treg phenotype	Prediction
	21	Race between CD25/STAT5 and mTOR pathway activation critical for early FOXP3 expression	Prediction
	22	Slower response to activation allows for differentiation intoTreg phenotype after Ag removal	Prediction
	23	Variability in timing of events combined with effective duration of receptor-antigen binding leads to mixed population	Prediction