T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function in mice.
Eur J Immunol
; 52(2): 312-327, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34752634
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
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Plasmodium falciparum
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Linfocitos T CD4-Positivos
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Antígenos CD
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Regulación de la Expresión Génica
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Malaria Falciparum
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Linfocitos T CD8-positivos
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Receptor de Muerte Celular Programada 1
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Tolerancia Inmunológica
Límite:
Adolescent
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Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Immunol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania