Adoptively transferred Th1 cell populations lose IFNgamma+ 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, IFNgamma production has been argued to define distinct Th1 lineages: whereas IFNgamma- Th1 cells survive and differentiate in vivo, IFNgamma+ Th1 cells eventually undergo apoptosis. Alternatively, lineage commitment might not be directly associated with the actual IFNgamma 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 IFNgamma+ within the Th1 cells declined by approximately 50%. This was not affected by the initial frequencies of IFNgamma+ cells within the transferred Th1 cell populations and by the presence of the antigen. Arguing against positive selection of IFNgamma non-producers in vivo, cell division rates of IFNgamma+ and IFNgamma- Th1 cells were comparable. Our data suggest that the 'loss' of IFNgamma+ 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 IFNgamma+ 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 IFNgamma- Th1 effector cells.