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PLoS One. 2019 Jun 28;14(6):e0219047. doi: 10.1371/journal.pone.0219047. eCollection 2019.

Innate-like T cells in children with sickle cell disease.

Author information

1
Department of General Pediatrics and Pediatric Infectious Diseases, Hôpital Necker-Enfants malades, Paris Descartes - Sorbonne Paris Cité University, Assistance Publique-Hôpitaux de Paris, Paris, France.
2
Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Inserm U1163, Paris, France.
3
Laboratory of Excellence GR-Ex, Paris, France.
4
Laboratory of Immunoregulation and Immunopathology, Institut Necker-Enfants malades, Centre National de la Recherche Scientifique (CNRS) UMR 8253, Inserm UMR 1151, Paris Descartes - Sorbonne Paris Cité University, Paris, France.
5
Department of Hematology, Hôpital Necker-Enfants malades, Paris Descartes - Sorbonne Paris Cité University, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

BACKGROUND:

The implication of lymphocytes in sickle cell disease pathogenesis is supported by a number of recent reports. These studies provided evidence for the activation of invariant natural killer T (iNKT) cells in adult patients, but did not investigate the involvement of other innate-like T cell subsets so far.

METHODS:

Here we present a monocentric prospective observational study evaluating the number and functional properties of both circulating conventional and innate-like T cells, namely iNKT, Mucosal-Associated Invariant T (MAIT) and gammadelta (γδ) T cells in a cohort of 39 children with sickle cell disease.

RESULTS:

Relative to age-matched healthy controls, we found that patients had a higher frequency of IL-13- and IL-17-producing CD4+ T cells, as well as higher MAIT cell counts with an increased frequency of IL-17-producing MAIT cells. Patients also presented increased Vδ2 γδ T cell counts, especially during vaso-occlusive crisis, and a lower frequency of IFNγ-producing Vδ2 γδ T cells, except during crisis. iNKT cell counts and the frequency of IFNγ-producing iNKT cells were unchanged compared to controls. Our study revealed positive correlations between 1) the frequency of IFNγ-producing CD4+, CD8+ and Vδ2 γδ T cells and the number of hospitalizations for vaso-occlusive crisis in the previous year; 2) the frequency of IFNγ-producing iNKT cells and patients' age and 3) the frequency of IL-17-producing Vδ2 γδ T cells and hemoglobin S level.

CONCLUSION:

These results strongly suggest a role of innate-like T cells in sickle cell disease pathophysiology, especially that of IL-17-producing MAIT and γδ T cells.

Conflict of interest statement

The authors have declared that no competing interests exist.

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