CD31 (PECAM-1) is a differentiation antigen lost during human CD4 T-cell maturation into Th1 or Th2 effector cells

The CD31 antigen (PECAM-1) has been reported to be a stable marker for a human CD4 T-cell subpopulation unable to produce interleukin-4 (IL-4). We show here that CD31 expression is not stable inasmuch as CD4 T-cell lines and clones derived from cell-sorted neonatal CD31(+) cells lose CD31 upon repetitive cycles of stimulation and IL-2 expansion. Moreover, various cytokines (IL-1 alpha, IL-4, IL-6, transforming growth factor-beta) fail to reinduce CD31 on CD31(-) clones. Whereas all CD31(+) CD4 T cells rapidly express high levels of the CD45RO antigen and downregulate the L-selectin antigen after priming, CD31 disappears more slowly because only part of the cells lose CD31 expression upon each cycle of stimulation. Loss of CD31 reflects a functional maturation of CD45RO(+) cells since, in a system which favours the development of Th2 effecters, IL-4 is produced by CD31(-) but not CD31(+) effector T cells, whereas interferon-gamma is produced by both types of cells. However, CD31 is not a Thl marker since it is not expressed on several Thl antigen-specific clones. We conclude that CD31 is a maturation marker expressed on the great majority of naive CD45RO(-) CD4 T cells and on a subset of CD45RO(+) CD4 T cells that are at an intermediate stage of maturation.