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Varying Immunizations With Plasmodium Radiation-Attenuated Sporozoites Alter Tissue-Specific CD8 + T Cell Dynamics.
- Source :
-
Frontiers in immunology [Front Immunol] 2018 May 28; Vol. 9, pp. 1137. Date of Electronic Publication: 2018 May 28 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Whole sporozoite vaccines represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosage and frequency, we systematically analyzed intrasplenic and intrahepatic CD8 <superscript>+</superscript> T cell responses following varied immunizations of mice with radiation-attenuated sporozoites. By combining experimental data and mathematical modeling, our analysis indicates a reversing role of spleen and liver in the generation of protective liver-resident CD8 <superscript>+</superscript> T cells during priming and booster injections: While the spleen acts as a critical source compartment during priming, the increase in vaccine-induced hepatic T cell levels is likely due to local reactivation in the liver in response to subsequent booster injections. Higher dosing accelerates the efficient generation of liver-resident CD8 <superscript>+</superscript> T cells by especially affecting their local reactivation. In addition, we determine the differentiation and migration pathway from splenic precursors toward hepatic memory cells thereby presenting a mechanistic framework for the impact of various vaccination protocols on these dynamics. Thus, our work provides important insights into organ-specific CD8 <superscript>+</superscript> T cell dynamics and their role and interplay in the formation of protective immunity against malaria.
- Subjects :
- Algorithms
Animals
Antigens, Protozoan immunology
CD8-Positive T-Lymphocytes metabolism
Female
Host-Pathogen Interactions immunology
Immunization
Immunologic Memory
Immunophenotyping
Liver immunology
Liver parasitology
Lymphocyte Count
Malaria prevention & control
Mice
Models, Biological
Models, Theoretical
Organ Specificity immunology
Plasmodium berghei immunology
Spleen immunology
Spleen parasitology
Vaccination
CD8-Positive T-Lymphocytes immunology
Malaria immunology
Malaria parasitology
Plasmodium immunology
Plasmodium radiation effects
Sporozoites immunology
Sporozoites radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 29892289
- Full Text :
- https://doi.org/10.3389/fimmu.2018.01137