In vitro studies of the relationship between tumor necrosis factor (TNF) and regulatory T (TREG) cells have produced contrasting results to date. Now, an in vivo mouse study published in The Journal of Immunology provides further insight into the potential link between these two key elements of the inflammatory response.

Biton et al. chose TNF-transgenic (hTNF-αTg) mice as a TNF-driven model of arthritis in which to study the development of TREG cells and also the effects of TNF blockade on these cells. First, they confirmed that hTNF-αTg mice develop arthritis from 8 weeks of age, and that this disease worsens as the mice age. Analysis of the number of TREG cells in these mice showed that after an initial reduction in comparison to wild-type mice at 7 weeks, the frequency of TREG cells increased to higher levels than seen in the wild-type mice at 24 weeks. The authors conclude that although numbers of TREG cells do recover in hTNF-αTg mice, once arthritis is established these cells are unable to control the inflammation.

Next, the authors used two approaches to block TNF: the anti-TNF antibody infliximab and also a TNF-kinoid, which actively induces expression of anti-TNF antibodies. Either treatment resulted in reduced severity of arthritis and also in increased numbers of TREG cells in comparison to no treatment. In addition, the TREG cells in the treated mice expressed higher levels of CTLA-4 than these cells in untreated mice, and a higher proportion of them was negative for CD62L, findings which suggest that TNF blockade has enhanced the suppressive capacity of the TREG cells in this mouse model.