Differential effects of anti-TNF alpha therapy on the immune cell compartment in Crohn’s disease patients

Anti-TNFα antibody treatment has revolutionized the management of Crohn’s disease (CD). Compared to treatment with corticosteroids or other commonly used anti-inflammatory agents in CD patients, the anti-TNFα agents are substantially more potent in inducing mucosal healing. The reasons for this are unknown and, somewhat surprisingly, also the exact anti-inflammatory mechanisms of anti-TNFα therapy remain elusive.

The aim of the present study was to investigate a potential change in the frequencies of immune cells in peripheral blood and the intestinal mucosa in CD as a result of three months anti-TNFα (adalimumab) treatment.

All patients responded to the adalimumab therapy, as evaluated by the Harvey-Bradshaw Index, and other clinical markers after three months of treatment. The flow cytometry results showed significant decreases in the percentages of Th1, Th17, Th17/Th1 cells as well as CD8⁺ IFNγ⁺ T cells in both peripheral blood and the gut mucosa. In contrast, the frequency of FoxP3⁺ regulatory T-cells remained unchanged throughout the treatment period. We also observed an increase in epithelial γδ T cells frequencies as a result of the adalimumab treatment. Interestingly, macroscopically non-inflamed intestinal segments showed similar trends or changes in immune cell composition as inflamed segments.

This study demonstrates that adalimumab treatment has considerable effects on the frequencies of proinflammatory T cell subsets, whereas regulatory T cell percentage is not significantly affected. Since the changes in immune cell composition correlated with the event of mucosal healing, it is possible that these changes are directly involved in the induction of wound healing.