CD4+CD25+CD127dimFoxp3+ T cells are cytotoxic for human neurons

Journal of Leukocyte Biology

Yohannes Haile¹  R. Chris Bleackley  and¹  Diane Turner¹  Fabrizio Giuliani¹  Dion Pasychniyk¹ 

[1] Division of Neurology/Department of Medicine and  Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada

关键词: granzyme B;    axonal injury;    cytotoxicity;    T_regs;    neurodegeneration;   

DOI  :  10.1189/jlb.1210654

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown