Beschreibung:
<jats:p>A CD8<jats:sup>+</jats:sup> T cell of naive phenotype has multiple career choices during its primary differentiation into an effector cell population. One of these career options is becoming a CD8<jats:sup>low</jats:sup> T cell. We have previously shown by <jats:italic>in vitro</jats:italic> studies that CD8<jats:sup>low</jats:sup> T cells have lost expression of CD8 surface protein and mRNA and are poorly cytolytic. In line with poor cytolytic function, CD8<jats:sup>low</jats:sup> T cells express low levels of perforin and granzyme B and C, mediators of the granule‐exocytosis machinery. However, CD8<jats:sup>low</jats:sup> T cells express IFN‐γ and substantial amounts of IL‐4, the signature cytokines of type 1 and type 2 T‐cell polarization, respectively. Here, we argue that the CD8<jats:sup>low</jats:sup> phenotype is an alternative career choice for any naive CD8<jats:sup>+</jats:sup> T cell during primary activation but that the probability of choosing this option is greatly enhanced by both IL‐4 and strong activation conditions. CD8<jats:sup>low</jats:sup> T cells have downregulated CD8α/β heterodimers and no preferential CD8α/α homodimer expression. As shown by anti‐CD8 Ab blocking experiments, surface CD8 substantially contributes to the CD8 T cell's effector function (i.e. cytokine expression and cytolytic activity). The distinct effector profile of CD8<jats:sup>low</jats:sup> T cells gives an example of the complexity of different CD8 T cell careers during primary effector differentiation.</jats:p>