PubMed日本語 - 熱帯熱マラリア原虫に対する長期被曝は、BとT細胞消耗の表現型証拠と関係している。―QLifePro医療翻訳医療翻訳 QLifePro



Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion.

Published date 2012 Dec 21

Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion.


Published date



Joseph Illingworth, Noah S Butler, Sophie Roetynck, Jedida Mwacharo, Susan K Pierce, Philip Bejon, Peter D Crompton, Kevin Marsh, Francis M Ndungu


Kenya Medical Research Institute, Centre for Geographical Medicine Research Coast, Kilifi, Kenya.


Naturally acquired immunity to malaria develops slowly, requiring several years of repeated exposure to be effective. The cellular and molecular factors underlying this observation are only partially understood. Recent studies suggest that chronic Plasmodium falciparum exposure may induce functional exhaustion of lymphocytes, potentially impeding optimal control of infection. However, it remains unclear whether the "atypical" memory B cells (MBCs) and "exhausted" CD4 T cells described in humans exposed to endemic malaria are driven by P. falciparum per se or by other factors commonly associated with malaria, such as coinfections and malnutrition. To address this critical question we took advantage of a "natural" experiment near Kilifi, Kenya, and compared profiles of B and T cells of children living in a rural community where P. falciparum transmission is ongoing to the profiles of age-matched children living under similar conditions in a nearby community where P. falciparum transmission ceased 5 y prior to this study. We found that continuous exposure to P. falciparum drives the expansion of atypical MBCs. Persistent P. falciparum exposure was associated with an increased frequency of CD4 T cells expressing phenotypic markers of exhaustion, both programmed cell death-1 (PD-1) alone and PD-1 in combination with lymphocyte-activation gene-3 (LAG-3). This expansion of PD-1-expressing and PD-1/LAG-3-coexpressing CD4 T cells was largely confined to CD45RA(+) CD4 T cells. The percentage of CD45RA(+)CD27(+) CD4 T cells coexpressing PD-1 and LAG-3 was inversely correlated with frequencies of activated and classical MBCs. Taken together, these results suggest that P. falciparum infection per se drives the expansion of atypical MBCs and phenotypically exhausted CD4 T cells, which has been reported in other endemic areas.


しかしながら、風土性のマラリアにさらされるヒトで述べられる「非定型」記憶B細胞(MBC)と「消耗した」CD4 T細胞が熱帯熱マラリア原虫自体によって、または、一般にマラリア(例えば同時感染と栄養失調症)と関連した他の因子によってドライブされるかどうかは、不明なままである。
持続的な熱帯熱マラリア原虫暴露は、リンパ球-活性化遺伝子-3(LAG-3)と結合して消耗、両方のプログラムされた細胞死亡-1(PD-1)単独とPD-1の表現型標識を表しているCD4 T細胞の増加した頻度と関係していた。
PD-1-expressingするこの展開とPD-1/LAG-3、- CD4 T細胞を同時発現することは、主にCD45RA(+) CD4 T細胞に限定された。
PD-1とLAG-3を同時発現しているCD45RA(+)CD27(+) CD4 T細胞のパーセンテージは、起動および古典的MBCの頻度と、反対に相関していた。
まとめると、これらの結果は熱帯熱マラリア原虫感染が非定型MBCと表現型的に消耗したCD4 T細胞の膨張をそれ自体は引き起こすことを示唆する。

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