While Treg exhibit an anergic phenotype in vitro, Treg proliferate in vivo at a rate similar to memory phenotype (MP; defined as CD44hi, CD62Llo) CD4+ T cells. In short-term BrdU labeling experiments, both populations uptake the label at a rate of 6% to 10% of cells in a 24-hour period. However, MP T cells are made up of multiple cell populations that proliferate at different rates and short-term labeling experiments only label the rapidly dividing population. To address whether Treg may also consist of multiple populations of cells dividing at different rates, we conducted long-term labeling experiments by providing BrdU in the drinking water. Adult thymectomized mice were used to control for new T cell development. In mice labeled for 20 days, only ~60% of the Treg were BrdU positive suggesting that a significant population of Treg is non-proliferative. BrdU incorporation was positively correlated with the level of CD44 expression on Treg and nondividing Treg uniquely expressed the cell surface marker Ly-6C. Ly-6C positivity represented a stable phenotype of Treg, as sorted Ly-6C negative and positive Treg retained their respective Ly-6C expression following adoptive transfer into a naïve host. These findings suggest that Treg are made up of rapidly dividing and quiescent subpopulations. The functional significance of these distinct populations is being investigated.
- Copyright © 2013 by The American Association of Immunologists, Inc.