Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria.
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 (CD44(hi)IL-7Rα(+)) developed during the chronic infection, and were readily distinguishable from effector (CD62L(lo)IL-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 (CD62L(lo)CD27(+)) 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, CD44(hi) 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.
MRC National Institute for Medical Research, London, UK.
Robin
R
Stephens
Jean
J
Langhorne
D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology / Q000637:transplantation; D004268:DNA-Binding Proteins / Q000502:physiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008288:Malaria / Q000276:immunology / Q000473:pathology; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016788:Plasmodium chabaudi / Q000254:growth & development / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004268:DNA-Binding Proteins; D020066:Merozoite Surface Protein 1; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D014409:Tumor Necrosis Factor-alpha; C415350:interleukin-7 receptor, alpha chain; D016753:Interleukin-10; D007371:Interferon-gamma