Children With Celiac Disease Have a Higher Degree of Activated or Exhausted <scp>CD4</scp>⁺ and <scp>CD8</scp>⁺ T Cells Compared to Healthy References

Type 1 diabetes (T1D) and celiac disease (CeD) are two chronic autoimmune disorders commonly diagnosed during childhood. In this exploratory study we performed flow cytometric immunophenotyping of various immune cell populations in peripheral blood from children with T1D, CeD, a T1D and CeD comorbidity, and from age-matched healthy references (controls). With extensive flow cytometry panels covering subpopulations of both CD4⁺ and CD8⁺ T cells, as well as monocytes and NK cells, our main finding is a tendency towards a higher degree of activated/exhausted T cells in children with a sole diagnosis of CeD compared with healthy references. This was seen through a higher fraction of CD4⁺ T cells positive for PD-1, CCR5 and CCR10, as well as a higher fraction of CD8⁺ T cells expressing PD-1 and CD39. In contrast, children with CeD showed a lower percentage of naïve CD8⁺ T cells compared with healthy references. Other important findings are a skewed CD4⁺/CD8⁺ ratio for children with a comorbidity compared with references, increased fractions of T regulatory cells (Tregs, CD4⁺CD25⁺CD127^low) for all three diagnosis groups compared with references, and a higher percentage of CD56^dimCD16⁺ NK cells with a corresponding lower percentage in CD56^dimCD16^- NK cells in CeD compared to the T1D and CeD comorbidity. Ultimately, analysis of the peripheral immunological milieu might lead to the development of more efficient tools for diagnosis and monitoring, and better treatment options, for children with T1D, CeD, and the rare combination of T1D and CeD.