Liang-Peng Yang

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‐1α, IL‐4, IL‐6, transforming growth factor‐β) fail to reinduce CD31 on CD31− clones. Whereas all CD31+ CD4 T cells rapidly express high levels of the CD45RO antigen and down‐regulate 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 effectors, IL‐4 is produced by CD31− but not CD31+ effector T cells, whereas interferon‐γ is produced by both types of cells. However, CD31 is not a Th1 marker since it is not expressed on several Th1 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.

OX40–Mediated Cosignal Enhances the Maturation of Naive Human CD4+ T Cells into High IL–4–Producing Effectors

Our previous studies have indicated that naive human CD4+ T cells of neonatal or adult origin may be the initial source of IL–4 which is required for their development into Th2 effectors. In addition to minute amounts of IL–4, anti–CD3/B7.1–activated naive cells also release readily detectable levels of IL–13 and IFN–γ. The production of IL–4 and IL–13 by naive T cells is differentially regulated by TGF–β and IL–12. Shortly after activation, naive T cells express surface OX40, a TNF–R family member whose ligand (OX40L) is constitutively expressed on a subset of dendritic cells. Engagement of OX40 on activated naive T cells increases their expression of IL–4 and IL–13, suppresses that of IFN–γ and promotes their development into Th2–like effectors.