A population of CD4hiCD38hi T cells correlates with disease severity in patients with acute malaria
Year: 2020
Type: article
Study design: Observational Study
Abstract: Objective CD4+ T cells are critical mediators of immunity to Plasmodium spp. infection, but their characteristics during malarial episodes and immunopathology in naturally infected adults are poorly defined. Flow cytometric analysis of PBMCs from patients with either P. falciparum or P. knowlesi malaria revealed a pronounced population of CD4+ T cells co‐expressing very high levels of CD4 and CD38 we have termed CD4hiCD38hi T cells. We set out to gain insight into the function of these novel cells. Methods CD4+ T cells from 18 patients with P. falciparum or P. knowlesi malaria were assessed by flow cytometry and sorted into populations of CD4hiCD38hi or CD4norm T cells. Gene expression in the sorted populations was assessed by qPCR and NanoString. Results CD4hiCD38hi T cells expressed high levels of CD4 mRNA and canonical type 1 regulatory T‐cell (TR1) genes including IL10, IFNG, LAG3 and HAVCR2 (TIM3), and other genes with relevance to cell migration and immunomodulation. These cells increased in proportion to malaria disease severity and were absent after parasite clearance with antimalarials. Conclusion In naturally infected adults with acute malaria, a prominent population of type 1 regulatory T cells arises that can be defined by high co‐expression of CD4 and CD38 (CD4hiCD38hi) and that correlates with disease severity in patients with falciparum malaria. This study provides fundamental insights into T‐cell biology, including the first evidence that CD4 expression is modulated at the mRNA level. These findings have important implications for understanding the balance between immunity and immunopathology during malaria.
DOI: 10.1002/cti2.1209
Institutions: QIMR Berghofer Medical Research Institute, Charles Darwin University, Menzies School of Health Research, Monash University, RMIT University, University of Tasmania, Mahidol University, University of Oxford, Mahidol Oxford Tropical Medicine Research Unit, Australian Institute of Tropical Health and Medicine, James Cook University
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Awards: G1617459808, Research Fellowship, Pathophysiology and treatment of malaria in our region, G4865280872, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Improving the treatment of Plasmodium vivax, G5403359577, G6001757730, Tropical diseases: Translating discoveries into better health, G675268645, G678660392, Risk factors, mechanisms, and treatment of knowlesi malaria, G7597818247, Tropical Disease - immunity, pathogenesis and vaccine development: global translation, Improving the treatment of Plasmodium vivax
OpenAlex ID: W3110033641