T cells are used in various therapies for the treatment of patients. For instance, the presence of T cells is an important factor in stem cell therapy of leukemia patients. Sometimes, umbilical cord blood is used as a source of stem cells. Correlative evidence suggested that the outcome of cord blood transplantation therapy was positively influenced by the presence, in the cord blood, of T cells derived from the mother of the cord blood donor. Here, we have attempted to isolate and characterize such maternal T cells in cord blood. In contrast to an earlier study, that reported the presence of relatively high numbers of maternal T cells in cord blood, we could not unequivocally detect and isolate such T cells, despite the use of various highly effective enrichment techniques. On the basis of these results (including some that were obtained through the use of a highly sensitive molecular detection technique) we conclude that maternal T cells are much less abundant in cord blood than previously reported, at least in the cohort of 30 cord bloods examined by us. This result makes it unlikely that the presence of maternal T cells in cord blood represents a biological phenomenon and, more importantly, that this is an important factor in determining the outcome of cord blood transplantation. It is, however, possible that the presence of maternal T cells in cord blood depends on special harvesting methods. It would therefore still be useful to measure the presence of maternal T cells in cord bloods to be used for stem cell transplantation. Regulatory T cells are a type of T cells that suppress the immune system. Because of this property, such cells are used in patients to prevent rejection of transplants as well as to mitigate autoimmune disease. It is not clear which type of Tregs is the best for such therapies. Experiments in mice have shown that some Tregs are unstable, causing them to lose their regulatory properties and even acquire the ability to exacerbate inflammatory disease. Distinguishing such unstable Tregs from stable ones has not been possible thus far. In a molecular analysis of Tregs, we identified a novel molecule that is expressed on the surface of a subset of Tregs in human blood. We found that the Tregs that express this molecule are more stable than those that do not. In addition, the presence of this molecule marks the presence of other desirable properties in Tregs, such as the capacity to proliferate robustly and to acquire specialized functions tailored for use in specific afflictions.

Thesis 2021: Still waters run deep: Making sense of (regulatory) T cell heterogeneity to improve adoptive cellular therapy, Rianne Opstelten