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

We compared naive 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+ naive CD4 T-cells but constant sjTRECs and constant naive CD4 T-cell numbers with age, together with increased Bcl-2 expression suggest increased TCR signaling with increased naive T-cell survival. We conclude PPMS patients have peripheral immune alterations related to reduced thymic output. (C) 2011 Elsevier B.V. All rights reserved.