Data from the Crohn’s and Treg Cells Study (CATS1) are very preliminary but indicate that administration of antigen-specific T-regulatory cells (Tregs) to refractory Crohn’s disease (CD) patients could be effective (Gastroenterol 2012; 143: 1207-17).  Tregs are specialized subpopulations of T-cells.

In this study, the investigators, performed a 12-week open-label multicenter single injections study of 20 patients with refractory CD.  After withdrawing blood from patients, mononuclear cells were isolated and cultured.  Subsequently, T cells were cloned.  A specific subset with high IL-10/IL-13 production and low IL-4 production were selected.

Key findings:

• 8 of 20 (40%) patients had a CDAI reponse at 5 and 8 weeks.  This was associated with a reduction in serum CRP and a trend of decreasing fecal calprotectin.
• Remission was noted in 3 patients at week 5 and in 2 patients at week 8.
• Overall, regardless of dose used, the safety profile was “in line” with severe active refractory CD.  Gastrointestinal adverse events were common.  7 patients had CD flares. One patient died due to suicide.

To understand this study more fully, an accompanying editorial is in the same issue (pages 1135-38).  A more complete discussion of the function of Treg cells is given, included their physiologic role of patrolling the gut lamina propia for antigens ‘derived from food and commensal flora.’  Circulating Treg cells may be deficient in IBD patients and thus contribute to the pathogenesis.

While injecting Treg cells may become a useful therapy, other ways of boosting Treg cells may be enhanced as an alternative.  Currently, granulocyte colony-stimulating factor (GCSF), anti-TNFα agents, and IL-2 all have the potential to enhance Treg cell function.  This supports the editorial’s conclusion that ‘Treg cells are rapidly moving from the bench to the bedside.’

Given the experimentation with stem cell therapy and bone marrow transplantation for CD, Treg cells show promise of a much more targeted effect on the immune system.

Additional references:

• -Blood 2010; 116:6123-32.  Autologus stem cell transplantation in patients with refractory CD.
• -Gut 2008; 57: 211-17.  Autologus stem cell transplantation for refractory CD.
• -Gut 2010; 59: 1662-69.  Mesenchymal stromal cell treatment for luminal Crohn’s.