Early Effector Cells Survive The Contraction Phase In Malaria Infection And Generate Both Central And Effector Memory T Cells
- ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
- Dr.. Michael Opata, Assistant Professor (Creator)
- Institution
- Appalachian State University (ASU )
- Web Site: https://library.appstate.edu/
Abstract: CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127-CD62LhiCD27+) are less divided than CD62Llo Teff and express memory genes. Intermediate (CD62LloCD27+) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62LloCD27-) late effector cells have a terminal Teff phenotype (PD-1+, Fashi, AnnexinV+). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation.
Early Effector Cells Survive The Contraction Phase In Malaria Infection And Generate Both Central And Effector Memory T Cells
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Additional Information
- Publication
- Michael M. Opata, Victor H. Carpio, Samad A. Ibitokou, Brian E. Dillon, Joshua M. Obiero, Robin Stephens; Early Effector Cells Survive the Contraction Phase in Malaria Infection and Generate Both Central and Effector Memory T Cells. J Immunol 1 June 2015; 194 (11): 5346–5354. Publisher version of record available at: https://doi.org/10.4049/jimmunol.1403216
- Language: English
- Date: 2015
- Keywords
- Malaria, T cells, CD antigens