Crohn’s disease appears to be caused by an excessive CD4+ T helper cell type I response directed against undefined antigens of the commensal bacterial flora.¹ T cells from affected areas of Crohn’s disease mucosa produce enhanced amounts of interferon γ (IFN-γ) and tumour necrosis factor α. Other markers of Th1 cells, such as expression of the transcription factor T-bet, the high affinity β2 chain of the interleukin 12 (IL-12) receptor, and activated STAT4, all indicate that the mucosal environment in Crohn’s disease favours Th1 polarisation.¹

It is important to emphasise that CD4 T cells in normal bowel are also Th1 skewed and express T-bet, so that the differences seen in Crohn’s disease are quantitative rather than qualitative.² Normal mucosal T cells are however susceptible to apoptosis, whereas this is not the case in Crohn’s disease,³ suggesting that it is the persistence and accumulation of Th1 cells which drives tissue injury.

Factors which commit virgin T cells to the Th1 or Th2 pathway are still under investigation. T-bet appears to be of primary importance.⁴ It is induced by IFN-γ itself and is capable of promoting IFN-γ production, not only in Th1 cells, but also in Th2 cells. T-bet also increases expression of the IL-12Rβ2 chain. Macrophage and dendritic cell derived IL-12 is crucial in Th1 immune responses.⁵ The …