Unraveling immune recovery after allogeneic hematopoietic stem cell transplantation: the contribution of flow cytometry

Allogeneic hematopoietic cell transplantation (allo-HCT) is frequently used as treatment for patients with hematological disorders. Main causes of failure of allo-HCT include disease relapse, graft-versus-host disease (GVHD) and infections, stressing the need for research focusing at immune reconstitution after allo-HCT. T cell recovery after allo-HCT depends on both homeostatic peripheral expansion (HPE) of donor T cells contained in the graft, and T cell neo-production from donor hematopoietic stem cells (thymo-dependent pathway). In young patients undergoing allo-HCT, most circulating T cells during the first months following allo-HCT are the progeny of T cells infused with the graft through HPE. Specifically, consequently to the lymphopenia caused by the conditioning regimen, IL-7 and IL-15 are not consumed and lead to different mechanisms of HPE according to the concerned cells. Beyond day 100, neo-generation of T cells by the thymus is progressively set up and plays an increasing role in reconstituting the T cell pool in patients younger than 60 years. Since HPE allows the expansion of non-tolerant T cells, it has been postulated that HPE is the driving force of graft-versus-tumor effects, but also of GVHD.
Regulatory T cells (Tregs) represent a fraction of CD4+ T cells that are indispensable for maintaining immunological self-tolerance. They constitutively express the forkhead box protein 3 factor (FoxP3) in their nuclei, and CD25 (the high-affinity component of the trimeric form of the interleukin 2 (IL-2) receptor) on their cell surface. Consequently, IL-2 is the key cytokine for Treg homeostasis. Interestingly, a deficit in Treg homeostasis has been demonstrated in patients with GVHD, and correction of the Treg homeostasis by low-dose IL-2 administration induced clinical responses in the majority of patients with GVHD.
The presentation will discuss how flow cytometry can be used to monitor T cell recovery after allo-HCT, with a special focus of new techniques allowing studying Treg reconstitution / homeostasis after allo-HCT.