The transcription factor Bach2 is required to delay effector differentiation and allow memory commitment of B cells and CD8 T cells. However, the function of Bach2 in conventional CD4 T cell responses is less well established.

To characterise the role of Bach2 in CD4 T cells in vivo, we utilised the SMARTA T cell receptor, specific for a lymphocytic choriomeningitis virus (LCMV) MHCII epitope. Congenically marked wild type (WT) and Bach2- deficient CD4+ SMARTA T cells were co-transferred into the same recipient mice and their responses to LCMV infection compared. Bach2-deficient antigen-specific responders initially resembled control cells in activation status, capacity for effector differentiation and division. However, following the peak of the response there was more than ten-fold loss of Bach2^-/- responder cells compared with controls, a defect that persisted into the memory phase. Further characterisation at and around the time of loss indicated that Bach2^-/- responder cells and WT controls were similar in cell cycling, metabolic fitness and effector differentiation.

To study this defect in a more controlled manner, we cultured WT and Bach2-deficient CD4 T cells in vitro. Bach2-deficient T cells initially upregulated markers of activation similar to WT controls, but progressed more slowly through division. Furthermore, Bach2-deficient cells expressed dramatically increased amounts of effector molecules, including IFNg, IL-17 and IL-10, paralleled by derepression of transcription factor Blimp1. In addition, we observed a severe impairment of FoxP3 upregulation in the absence of Bach2. A loss of these cells in vitro at a similar time post stimulation to in vivo cells indicates an underlying requirement for Bach2 for the survival of CD4 T cells in allowing their continued response to antigen and their subsequent memory generation. Study on the molecular basis of this requirement is ongoing.