T-cells Promote Inflammation in Children with Sickle Cell as well as Adults, Study Finds

Children with sickle cell disease, like adults, have a distinct group of immune cells, called innate like T-cells, that appear to promote the chronic inflammation associated with SCD, researchers report.

Their work “Innate-like T cells in children with sickle cell disease” was published in the journal PLOS One.

Previous research has shown that adults with SCD have higher levels of innate like T-cells or ILTs, a group of white blood cells in the immune system.

ILTs include subgroups of other cells, namely the invariant natural killer T-cells (iNKT), mucosal-associated invariant T-cells (MAIT) and gammadelta T-cells.

These cells carry features of both the innate (general defense) and the adaptive (specialized) immune system. Growing evidence suggests these cells also play a role in inflammatory diseases, as they can produce pro-inflammatory cytokines like interleukin (IL)-17.

Adults with SCD, compared to healthy adults, are reported to have higher that usual levels of pro-inflammatory ILT cells and pro-inflammatory cytokines during vaso-occlusive crises (VOC), a hallmark feature of SCD linked with severe pain due to blocked blood vessels.

Whether such differences exist in children is unknown.

To understand the role of ILT cells in pediatric SCD, a team of French researchers collected blood samples from 39 children with sickle cell (median age, 12.4) and 11 age-matched controls.

Twenty three of the SCD children were being treated with daily doses of hydroxyurea, a medicine used to lessen the frequency of pain crises in SCD, and had been for a median of 3.5 years. Twelve were taking part in a blood transfusion program and had for a median 4.6 years.

Analysis of immune cells present in the blood samples found that these young SCD patients had MAIT cells that produced the IL-17 cytokine at higher frequencies, as well as elevated levels of gammadelta T-cells compared to healthy children. Levels of iNKT cells showed no differences relative to controls.

“These results are consistent with an involvement of innate-like T cells in SCD,” the researchers wrote.

Children experiencing a VOC had a higher level of circulating IFN-gamma compared to those not in a crisis state. Moreover, increased IFN-gamma production correlated with a greater number of hospitalizations for VOC.

Cytokine analysis revealed excessive IL-17 production by CD4 positive T-cells, as well as MAIT and gammadelta T-cells in the patient group relative to healthy children.

Researchers believe that while IFN gamma production contributes to vaso-occlusive crises, IL-17 promotes a chronic pro-inflammatory state in sickle cell patients.

This work “opens new perspectives for the study of innate-like T cells and Th17 cells, as likely important actors of SCD,” the study concluded.