Publication: A population of CD4<sup>hi</sup>CD38<sup>hi</sup> T cells correlates with disease severity in patients with acute malaria
Issued Date
2020-01-01
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20500068
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2-s2.0-85096625654
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical and Translational Immunology. Vol.9, No.11 (2020)
Suggested Citation
Simon H. Apte, Gabriela Minigo, Penny L. Groves, Jessie C. Spargo, Magdalena Plebanski, Mathew J. Grigg, Enny Kenangalem, Julie G. Burel, Jessica R. Loughland, Katie L. Flanagan, Kim A. Piera, Timothy William, Ric N. Price, Tonia Woodberry, Bridget E. Barber, Nicholas M. Anstey, Denise L. Doolan A population of CD4<sup>hi</sup>CD38<sup>hi</sup> T cells correlates with disease severity in patients with acute malaria. Clinical and Translational Immunology. Vol.9, No.11 (2020). doi:10.1002/cti2.1209 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/60504
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Title
A population of CD4<sup>hi</sup>CD38<sup>hi</sup> T cells correlates with disease severity in patients with acute malaria
Other Contributor(s)
Menzies School of Health Research
QIMR Berghofer Medical Research Institute
James Cook University
Monash University
University of Tasmania
Mahidol University
RMIT University
Nuffield Department of Medicine
Charles Darwin University
The Prince Charles Hospital
La Jolla Institute for Immunology
Papuan Health and Community Development Foundation
QIMR Berghofer Medical Research Institute
James Cook University
Monash University
University of Tasmania
Mahidol University
RMIT University
Nuffield Department of Medicine
Charles Darwin University
The Prince Charles Hospital
La Jolla Institute for Immunology
Papuan Health and Community Development Foundation
Abstract
© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc. 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.