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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function in mice
European Journal of Immunology, Volume 52, No. 2, Year 2022
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Description
Overwhelming activation of T cells in acute malaria is associated with severe outcomes. Thus, counter-regulation by anti-inflammatory mechanisms is indispensable for an optimal resolution of disease. Using Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice, we performed a comprehensive analysis of co-inhibitory molecules expressed on CD4+ and CD8+ T cells using an unbiased cluster analysis approach. We identified similar T cell clusters co-expressing several co-inhibitory molecules like programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) in the CD4+ and the CD8+ T cell compartment. Interestingly, despite expressing co-inhibitory molecules, which are associated with T cell exhaustion in chronic settings, these T cells were more functional compared to activated T cells that were negative for co-inhibitory molecules. However, T cells expressing high levels of PD-1 and LAG-3 also conferred suppressive capacity and thus resembled type I regulatory T cells. To our knowledge, this is the first description of malaria-induced CD8+ T cells with suppressive capacity. Importantly, we found an induction of T cells with a similar co-inhibitory rich phenotype in Plasmodium falciparum-infected patients. In conclusion, we demonstrate that malaria-induced T cells expressing co-inhibitory molecules are not exhausted, but acquire additional suppressive capacity, which might represent an immune regulatory pathway to prevent further activation of T cells during acute malaria. © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
Authors & Co-Authors
Kaminski, Lea Christina
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Schulze-Zur-Wiesch, Julian
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
German Center for Infection Research
Addo, Marylyn Martina
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
German Center for Infection Research
Ramharter, Michael
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Mackroth, Maria Sophia
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Hamburg
German Center for Infection Research
Jacobs, Thomas
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Germany, Hamburg
German Center for Infection Research
Riehn, Mathias
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Statistics
Citations: 8
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1002/eji.202149424
ISSN:
00142980
Research Areas
Genetics And Genomics
Infectious Diseases