Reduced thymic output and peripheral naïve CD4 T-cell alterations in primary progressive multiple sclerosis (PPMS)

Abstract

We compared naïve CD4 and CD8 T-cell homeostasis in primary progressive multiple sclerosis (PPMS), relapsing–remitting MS (RRMS) and controls. Quantitation of signal joint T-cell receptor (TCR) excision circles (sjTRECs) and quantitative estimates of daily thymic export confirm our previous report of reduced thymic output in RRMS and demonstrate reduced thymic output in PPMS. In PPMS, the decreasing % CD31+ naïve CD4 T-cells but constant sjTRECs and constant naïve CD4 T-cell numbers with age, together with increased Bcl-2 expression suggest increased TCR signaling with increased naïve T-cell survival. We conclude PPMS patients have peripheral immune alterations related to reduced thymic output.