Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate Commitment? Complexities of Interpretation due to the Heterogeneity of Memory CD4 T Cells, Including T Follicular Helper Cells

Plasticity is the ability of a cell type to convert to another cell type. There are multiple effector CD4 T-cell subtypes, including T(H)1, T(H)2, T(H)17, T(H)1*, CD4 CTL, T(H)9, and T-FH cells. It is commonly thought that a CD4 T cell can readily show full plasticity-full conversion from one differentiated cell-and this propensity to plasticity is possessed by memory CD4 T cells. However, there remains no direct demonstration of in vivo-generated resting memory CD4 T-cell conversion to a different subtype on secondary antigen challenge in vivo in an intact animal at the single-cell level. What has been clearly shown is that CD4 T cells possess extraordinary capacity for phenotypic heterogeneity, but that is a distinct property from plasticity. Heterogeneity is diversity of the resting memory CD4 T-cell population, not conversion of a single differentiated cell into another subtype. Apparently, plasticity at the population level can be accomplished by either mechanism, as heterogeneity of CD4 T-cell subpopulations could affect large shifts in subtype distribution at the overall population level via differential exponential expansion and death.