Early Effector cells Survive the Contraction Phase in Malaria Infection and Generate both Central and Effector Memory T cells
| Autor: | Brian E. Dillon, Joshua M. Obiero, Samad Ibitokou, Robin Stephens, Victor H. Carpio, Michael M. Opata |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Interleukin 2
CD4-Positive T-Lymphocytes Adoptive cell transfer medicine.medical_treatment Cellular differentiation Immunology Mice Transgenic Lymphocyte Activation Article Plasmodium chabaudi Interleukin-7 Receptor alpha Subunit Interferon-gamma Mice T-Lymphocyte Subsets medicine Immunology and Allergy Animals Interferon gamma L-Selectin Interleukin-7 receptor Merozoite Surface Protein 1 Mice Inbred BALB C biology Effector Cell Differentiation biology.organism_classification Adoptive Transfer Malaria Tumor Necrosis Factor Receptor Superfamily Member 7 Mice Inbred C57BL Cytokine Cytokines Interleukin-2 Immunologic Memory medicine.drug |
| Popis: | 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. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection. |
| Databáze: | OpenAIRE |
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