Changes in Thymopoiesis in Myasthenia Gravis

Abstract

This study was undertaken to investigate T-cell maturation in hyperplastic thymi of patients suffering from myasthenia gravis (MG). For this purpose, the expression of the major differentiational molecules (CD4, CD8, and CD3/TCRαβ) and that of the regulatory and activation molecules on thymocytes from MG patients and control subjects were estimated by flow cytometric analysis. In the MG patients the increase in relative proportion of immature (CD4−8− TCRαβ⁻) and the most mature (CD4+8− TCRαβ^high and CD4−8− TCR^high encompassing immunoregulatory NKT) thymocytes followed by a decrease in that of CD4+8+CD3⁻/TCRαβ⁻ cells was found. Furthermore, in these patients the relative proportion of CD4+HLA-DR+ and CD4+71+ cells was increased, whereas that of CD4+25+ cells was slightly, but significantly, decreased (reflecting, most likely, decreased contribution of T reg cells bearing this phenotype). Moreover, in MG thymi the percentage of CD45RA+ cells was reduced indicating changes in the selection processes. In keeping with this finding the reduced thymocyte apoptotic index and percentage of cells bearing apoptosing (CD4−8− TCRαβ^low) phenotype were detected. In conclusion, the study demonstrates substantial changes in intrathymic differentiation of T cells in hyperplastic MG thymi and suggests alterations in selection events providing an increased escape of potentially autoreactive T-cell clones, on one side, and an altered maturation and/or selection of immunoregulatory cells (NKT and CD4+8−25+ T reg cells) keeping these cell clones under control, on the other side.

Keywords:

• immunoregulatory cells
• myasthenia gravis
• T-cell maturation