Adoptively transferred Th1 cell populations lose IFNγ+ cells by cytokine down-regulation on single-cell level

Against the background of effector T cell heterogenity in terms of their in situ cytokine expression, IFNγ production has been argued to define distinct Th1 lineages: whereas IFNγ− Th1 cells survive and differentiate in vivo, IFNγ+ Th1 cells eventually undergo apoptosis. Alternatively, lineage commitment might not be directly associated with the actual IFNγ production. To address this issue, we adoptively transferred in vitro-polarized Th1 cell populations. Although absolute numbers of total Th1 cells after 3 days in vivo remained unchanged, numbers of IFNγ+ within the Th1 cells declined by approximately 50%. This was not affected by the initial frequencies of IFNγ+ cells within the transferred Th1 cell populations and by the presence of the antigen. Arguing against positive selection of IFNγ non-producers in vivo, cell division rates of IFNγ+ and IFNγ− Th1 cells were comparable. Our data suggest that the 'loss' of IFNγ+ cells within the transferred Th1 cell population might be rather caused by down-regulation of the cytokine expression on single-cell level than by deletion of individual IFNγ+ cells. Thus, our findings are more in line with the hypothesis that actual cytokine expression does not define distinct differentiation states and polarization-specific genes remain accessible also in IFNγ− Th1 effector cells.