Effector Memory Th1 CD4 T Cells Are Maintained in a Mouse Model of Chronic Malaria

PLoS Pathogens

Robin Stephens¹  Jean Langhorne¹ 

[1] Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom

关键词: Memory T cells;    T cells;    Parasitic diseases;    Malaria;    Cytokines;    Parasitemia;    Cell cycle;    cell division;    Cell differentiation;   

DOI  :  10.1371/journal.ppat.1001208

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Protection against malaria often decays in the absence of infection, suggesting that protective immunological memory depends on stimulation. Here we have used CD4+ T cells from a transgenic mouse carrying a T cell receptor specific for a malaria protein, Merozoite Surface Protein-1, to investigate memory in a Plasmodium chabaudi infection. CD4+ memory T cells (CD44hiIL-7Rα+) developed during the chronic infection, and were readily distinguishable from effector (CD62LloIL-7Rα−) cells in acute infection. On the basis of cell surface phenotype, we classified memory CD4+ T cells into three subsets: central memory, and early and late effector memory cells, and found that early effector memory cells (CD62LloCD27+) dominated the chronic infection. We demonstrate a linear pathway of differentiation from central memory to early and then late effector memory cells. In adoptive transfer, CD44hi memory cells from chronically infected mice were more effective at delaying and reducing parasitemia and pathology than memory cells from drug-treated mice without chronic infection, and contained a greater proportion of effector cells producing IFN-γ and TNFα, which may have contributed to the enhanced protection. These findings may explain the observation that in humans with chronic malaria, activated effector memory cells are best maintained in conditions of repeated exposure.

【 授权许可】

CC BY