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一個國際研究小組23日說，他們找到了一種名為Treg的免疫細胞（全稱為調(diào)節(jié)性T細胞），會使瘧疾患者病情轉(zhuǎn)為惡性。研究人員解釋說，這是因為Treg細胞會“關閉”人的免疫系統(tǒng)功能，使瘧原蟲不受控制地增長。 來自澳大利亞和印度尼西亞的研究人員在新一期美國《科學公共圖書館病原體卷》雜志上報告說，他們一共研究了33名瘧疾患者，都來自印度尼西亞的巴布亞省，其中16人患有惡性瘧疾，結果發(fā)現(xiàn)，這16名惡性瘧疾患者體內(nèi)都有相當多的Treg細胞。 負責這項研究的澳大利亞莫納什大學教授瑪格達萊娜·普萊班斯基說，這種細胞可高水平表達包括TNFRII在內(nèi)的表面標志物，從而抑制殺滅瘧原蟲的免疫反應。她說，有些人感染瘧疾后容易痊愈，有些人卻發(fā)展為惡性瘧疾而死亡，但科學家一直都不清楚其中的原因，新發(fā)現(xiàn)將為開發(fā)治療瘧疾的新藥物和免疫療法帶來希望。 瘧疾是由瘧原蟲引發(fā)、通過蚊子叮咬傳播的傳染病。據(jù)統(tǒng)計，全球每年有近5億人感染瘧疾，約100萬人死于瘧疾。長期以來，醫(yī)學界一直致力于瘧疾疫苗開發(fā)，但進展總體緩慢。 推薦原始出處： 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. (責任編輯：Doctor001) |
