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
✍ Scribed by Dupeh R. Palmer; Urszula Krzych
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 175 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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 ( + -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 pRBCstimulated 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 Agdriven 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.