Limited Role of CD4(+)Foxp3(+) Regulatory T Cells in the Control of Experimental Cerebral Malaria

作者：Steeg Christiane; Adler Guido; Sparwasser Tim; Fleischer Bernhard; Jacobs Thomas^*

来源：The Journal of Immunology, 2009, 183(11): 7014-7022.

DOI：10.4049/jimmunol.0901422

Cerebral malaria (CM) associated with Plasmodium berghei ANKA (PbA) infection is an accepted model of human CM. CM during PbA infection critically depends on sequestration of T cells into the brain. Several studies aimed to address the role of regulatory T cells (T-reg) in modulating this pathogenic T cell response. However, these studies are principally hampered due to the fact that until recently no reagents were available to deplete Foxp3(+) T-reg specifically. To study the function of T-reg in the genesis of CM, we used depletion of T-reg mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin receptor-enhanced GFP fusion protein under the control of the foxp3 gene locus. These mice allow for a selective depletion of Foxp3(+) T-reg by diphtheria toxin injection, and also their specific detection and purification during an ongoing infection. Using depletion of T-reg mice, we found only a small increase in the absolute numbers of Foxp3(+) T-reg during PbA infection and, consequently, the ratio of T-reg to T effector cells (T-eff) decreased due to the rapid expansion of T-eff, Although the latter sequester in the brains of infected mice, almost no T-reg were found in the brains of infected mice. Furthermore, we demonstrate that depletion of T-reg has no influence on sequestration of T-eff and on the clinical outcome, and only minor influence on T cell activation. Using ex vivo analysis of purified T-reg from either naive mice or PbA-infected mice, we found that both exhibit similar inhibitory capacity on T-eff The Journal of Immunology, 2009, 183: 7014-7022.

• 出版日期2009-12-1