TBET‐expressing Th1 CD4+ T cells accumulate in chronic lymphocytic leukaemia without affecting disease progression in Eµ‐TCL1 mice.

Summary: Chronic lymphocytic leukaemia (CLL) is associated with alterations in T cell number, subset distribution and function. Among these changes, an increase in CD4+ T cells was reported. CD4+ T cells are a heterogeneous population and distinct subsets have been described to exert pro‐ and anti‐tumour functions. In CLL, controversial reports describing the dominance of IFNγ‐expressing Th1 T cells or of IL‐4‐producing Th2 T cells exist. Our study shows that blood of CLL patients is enriched in Th1 T cells producing high amounts of IFNγ. Moreover, we observed that their frequency remains relatively stable in CLL patients over a time course of five years. Furthermore, we provide evidence for an accumulation of Th1 T cells in the Eµ‐TCL1 mouse model of CLL. As TBET (encoded by Tbx21) is a crucial transcription factor for Th1 polarization, we generated Tbx21−/− bone marrow chimaeric mice which showed a lower number of IFNγ‐producing Th1 T cells, and used them for adoptive transfer of Eµ‐TCL1 leukaemia. Disease development in these mice was, however, comparable to that in wild‐type controls, excluding a major role for TBET‐expressing Th1 cells in Eµ‐TCL1 leukaemia. Collectively, our data highlight that Th1 T cells accumulate in CLL but reducing their number has no impact on disease development. [ABSTRACT FROM AUTHOR]