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一个国际研究小组23日说，他们找到了一种名为Treg的免疫细胞（全称为调节性T细胞），会使疟疾患者病情转为恶性。研究人员解释说，这是因为Treg细胞会“关闭”人的免疫系统功能，使疟原虫不受控制地增长。 来自澳大利亚和印度尼西亚的研究人员在新一期美国《科学公共图书馆病原体卷》杂志上报告说，他们一共研究了33名疟疾患者，都来自印度尼西亚的巴布亚省，其中16人患有恶性疟疾，结果发现，这16名恶性疟疾患者体内都有相当多的Treg细胞。 负责这项研究的澳大利亚莫纳什大学教授玛格达莱娜·普莱班斯基说，这种细胞可高水平表达包括TNFRII在内的表面标志物，从而抑制杀灭疟原虫的免疫反应。她说，有些人感染疟疾后容易痊愈，有些人却发展为恶性疟疾而死亡，但科学家一直都不清楚其中的原因，新发现将为开发治疗疟疾的新药物和免疫疗法带来希望。 疟疾是由疟原虫引发、通过蚊子叮咬传播的传染病。据统计，全球每年有近5亿人感染疟疾，约100万人死于疟疾。长期以来，医学界一直致力于疟疾疫苗开发，但进展总体缓慢。 推荐原始出处： PLoS Pathogens April 2009 doi:10.1371/journal.ppat.1000402 Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria Gabriela Minigo1,2#, Tonia Woodberry2#, Kim A. Piera2, Ervi Salwati3, Emiliana Tjitra3, Enny Kenangalem4, Ric N. Price2,5, Christian R. Engwerda6, Nicholas M. Anstey2?, Magdalena Plebanski1?* 1 Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Australia, 2 International Health Division, Menzies School of Health Research (MSHR) and Charles Darwin University, Darwin, Australia, 3 National Institute of Health Research and Development (NIHRD), Ministry of Health, Jakarta, Indonesia, 4 NIHRD-MSHR Collaborative Research Program and District Health Authority, Timika, Papua, Indonesia, 5 Centre for Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, United Kingdom, 6 Queensland Institute of Medical Research, Brisbane, Australia Severe Plasmodium falciparum malaria is a major cause of global mortality, yet the immunological factors underlying progression to severe disease remain unclear. CD4+CD25+ regulatory T cells (Treg cells) are associated with impaired T cell control of Plasmodium spp infection. We investigated the relationship between Treg cells, parasite biomass, and P. falciparum malaria disease severity in adults living in a malaria-endemic region of Indonesia. CD4+CD25+Foxp3+CD127lo Treg cells were significantly elevated in patients with uncomplicated (UM; n = 17) and severe malaria (SM; n = 16) relative to exposed asymptomatic controls (AC; n = 10). In patients with SM, Treg cell frequency correlated positively with parasitemia (r = 0.79, p = 0.0003) and total parasite biomass (r = 0.87, p<0.001), both major determinants for the development of severe and fatal malaria, and Treg cells were significantly increased in hyperparasitemia. There was a further significant correlation between Treg cell frequency and plasma concentrations of soluble tumor necrosis factor receptor II (TNFRII) in SM. A subset of TNFRII+ Treg cells with high expression of Foxp3 was increased in severe relative to uncomplicated malaria. In vitro, P. falciparum–infected red blood cells dose dependently induced TNFRII+Foxp3hi Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive activity than TNFRII− Treg cells. The selective enrichment of the Treg cell compartment for a maximally suppressive TNFRII+Foxp3hi Treg subset in severe malaria provides a potential link between immune suppression, increased parasite biomass, and malaria disease severity. The findings caution against the induction of TNFRII+Foxp3hi Treg cells when developing effective malaria vaccines. (责任编辑：Doctor001) |
