Authors:
Yohannes Haile, Dion Pasychniyk, Diane Turner, R. Chris Bleackley, and Fabrizio Giuliani
Summary:
MS lesions are characterized by destruction of myelin and significant neuronal and axonal loss. Preliminary studies with the use of Tregs in the mouse model of MS have been extremely encouraging. However, recent studies with human cells have shown the presence of different subpopulations of T cells within the CD4+CD25+Foxp3+ T cell phenotype, some of which do not have regulatory functions. These findings suggest a potential difference between mouse and human in the regulatory phenotype. Here, we show that human activated CD4+CD25+Foxp3+ T cells are neurotoxic in vitro. These cells expressed high levels of the cytotoxic molecule GrB and had no suppressive effect. On the contrary, they produced IFN-γ and low IL-17, suggesting a shift toward a TH1 phenotype. Thus, our data confirm the presence of a nonregulatory cytotoxic subpopulation within the human CD4+CD25+Foxp3+ T cells and suggest further studies on the human regulatory phenotype prior to any potential therapeutic application.
Source:
Journal of Leukocyte Biology; Vol. 89, No. 6, 927-934 (03/14/11)