The hypoxia affects the main thymocyte subset distributions in congenital heart diseases
Congenital heart diseases (CHD) are often associated with thymus development disorders and immune dysfunctions. However, the features of thymocyte differentiation in cyanotic and acyanotic CHD remain unknown.
Materials and Methods: We have analyzed the main thymocyte subsets depending on CD4 and CD8 co-expression, and the number of natural regulatory T-cells (nTreg) and invariant natural killer T-cells (iNKT) precursors in the co-cultures of thymocytes with thymic plasmacytoid (p) dendritic cells (DCs) in vitro, isolated from the thymus of children with acyanotic (without hypoxia) and cyanotic (with severe hypoxia) CHD.
Results: In the thymocyte co-cultures with pDCs in cyanotic CHD, compared to acyanotic CHD, a decreased number of thymocytes expressing αβ chains of the T-cell receptor with CD4 and CD8 lower levels (CD4loCD8loαβTCR+), but the increased numbers of CD4hiCD8-/loαβTCR+ cells were detected. The numbers of CD4-CD8-αβTCR+, CD4hiCD8hiαβTCR+, CD4-/loCD8hiαβTCR+ cells did not differ between cyanotic or acyanotic CHD. In cyanotic CHD in the thymocyte co-cultures with pDCs, the decreased number of CD4+CD25+FOXP3+ cells, nTreg precursors, was detected in comparison with acyanotic CHD. In cyanotic CHD, the number of CD3hiVα24Jα18+ cells, iNKT precursors, in the thymocyte co-cultures with pDCs did not differ in comparison with acyanotic CHD. Hypoxia in cyanotic CHD increased the resistance to apoptosis of thymocytes in co-cultures with pDCs in comparison with acyanotic CHD. Conclusion: Thus, hypoxia affected the main CD4+ and CD8+ αβTCR T-cell subsets and the number of CD4+CD25+FOXP3+ cells in the thymocyte co-cultures with pDCs isolated from thymus of children with CHD.