Toward standardization of FoxP3+ regulatory T-cell measurement in clinical settings

Regulatory T-cells (T-regs) are a specialized subpopulation of T lymphocytes that act to suppress activation of other immune cells and to maintain immune system homeostasis, self tolerance, as well as to prevent excessive immune responses to foreign antigens. Over the last few years, evidence from both humans and animal models has accumulated that this cell subpopulation may play an important role in the pathogenesis of several diseases, suggesting that T-regs may be manipulated to treat those human diseases in the pathogenesis of which theyare implicated. Several reports provided evidence that autologous stem cell transplantation for autoimmune diseases may induce immunologic self-tolerance by reprogramming autoreactive T cells, thus restoring the immune regulatory network. The recent demonstration that T-regs could separate graft versus host disease from graft versus tumor reactivity represent another field in which the assessment of FoxP3þ T-regs play a role, and suggests that their immunosuppressive potential might be manipulated. Inhibition and depletion of T-reg inhibition represent another field of intervention in cancer immunotherapy. Furthermore, several studies also indicate that a defective T regulatory cell compartment can be modulated by B cell-targeted therapy or by antithymocyte globulin treatment, thus opening new scenarios in the treatment of various hematological malignancies as well as autoimmune diseases. To conclude, we believe that the article by Grant et al. furthers our insight on the characterization and enumeration of fresh and cryopreserved FoxP3-expressing T-regs in clinical samples; it should be kept in mind that the immunophenotypic profile of this cell subpopulation may vary significantly in cell culture over time, as a loss of FoxP3 expression after in vitro expansion of human CD4þ/CD25þ T-regs was recently documented. Such results illustrate the need for careful monitoring of T-regulatory cell populations in the setting of cellular therapeutic protocols where these may have an impact on disease outcome.