Because of limitations related to Treg cell detection in stored tissue samples, the investigators collected fresh intestinal tissue samples from babies having surgery for NEC and for non-NEC problems, during or immediately after surgery.
Using multiple cellular "markers" and flow cytometry to identify the Treg cells, they confirmed that premature babies have an abundance of Treg cells in the intestines. Babies with NEC had about 60 percent fewer Treg cells than babies with non-NEC problems.
The investigators also detected increased expression of inflammatory cytokines (immune system signaling molecules) particularly those that suppress Treg cell development in the NEC tissue samples. And in assays of cell function, they found that the Treg cells suppressed cytokine production by and proliferation of T cells.
Follow-up studies on tissue samples from infants who had a second surgery suggest that the reduction in Treg cells is not because of an immune system defect in the babies.
"We believe that the T regulatory cells we've identified are in fact functional Treg cells and that they are down-regulated at the time of NEC," Weitkamp said. "Our studies challenge the dogma that cellular immunity is not important in the immediate neonatal period or in the pathophysiology of NEC."
Now, Weitkamp and his colleagues including neonatology fellow Joann Romano-Keeler, M.D., are studying the intestinal microbiome the collection of microbes colonizing the gut in the surgically removed samples.
"We know that the microbiome and the immune system are important in shaping each other," Weitkamp said.
"We need to understand exactly how that works and which components typically found i
|Contact: Leigh MacMillan|
Vanderbilt University Medical Center