Cellular and molecular requirements for the recall of IL-4-producing memory CD4(+)CD45RO(+)CD27(-) T cells during protection induced by attenuated Plasmodium falciparum sporozoites.
The requirements for maintenance of antigen (Ag)-specific memory T cells in protection to malaria is poorly understood. We have previously demonstrated a recall of IL-4-producing memory CD4(+)CD45RO(+) T cells with parasitized red blood cells (pRBC) in persons protected by radiation-attenuated Plasmodium falciparum sporozoites (gamma-spz). Using the CD27 marker, we have now identified two subsets of CD4(+)CD45RO(+) T cells: CD4(+)CD45RO(+)CD27(+) T cells representing an early memory and CD4(+)CD45RO(+)CD27() T cells representing a terminally differentiated memory cells. A small subset of CD4(+)CD45RO(+)CD27(-) T cells also expressed CD70, the CD27 ligand. The addition of anti-CD70 monoclonal antibody (mAb) to pRBC-stimulated cultures significantly inhibited the conversion of CD27(+) to CD27(-) subset without profoundly affecting IL-4 production. In contrast, the inclusion of anti-CD27 mAb in parallel cultures abrogated IL-4 production without interfering with conscription of T cells into the CD27(-) T cell set. We propose that the persistence of memory CD4(+) T cells depends on Ag-driven conscription of a mature memory phenotype through co-ligation of CD27 and CD70 expressed, respectively, on CD27(+) and CD27(-) T cells. Hence, protracted protection in malaria depends in part on memory CD4(+) T cells that require specific Ag presumably from the repositories of liver-and blood-stage antigens and the delivery of a second signal from the CD27:CD70 interaction.
Palmer
Dupeh R
DR
Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Krzych
Urszula
U
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D053282:CD27 Ligand; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology; D009033:Culicidae / Q000469:parasitology; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007299:Insect Bites and Stings / Q000469:parasitology; D015847:Interleukin-4 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008024:Ligands; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D008024:Ligands; D017780:Malaria Vaccines; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014613:Vaccines, Attenuated; D015847:Interleukin-4; D017493:Leukocyte Common Antigens