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Cold Spring Harb Perspect Biol. 2018 Mar 1;10(3). pii: a032102. doi: 10.1101/cshperspect.a032102.

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.

Crotty S1,2,3.

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Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037.
Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, California 92037.
Department of Medicine, Division of Infectious Diseases, University of California, San Diego, La Jolla, California 92093.


Plasticity is the ability of a cell type to convert to another cell type. There are multiple effector CD4 T-cell subtypes, including TH1, TH2, TH17, TH1*, CD4 CTL, TH9, and TFH 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.

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