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Thymic involution and proliferative T-cell responses in multiple sclerosis.

Research paper by Danielle A DA Duszczyszyn, Julia L JL Williams, Helen H Mason, Yves Y Lapierre, Jack J Antel, David G DG Haegert

Indexed on: 13 Mar '10Published on: 13 Mar '10Published in: Journal of Neuroimmunology



Abstract

We investigated naïve CD4 T-cell homeostasis in relapsing-remitting multiple sclerosis (RRMS). Quantification of signal joint T-cell receptor excision circles in FACS-isolated CD31hi cells, which correspond closely to CD4 recent thymic emigrants (RTEs), indicates that young patients have reduced generation of CD4 RTEs compared to age-matched controls. In RRMS, compared to controls, CXCR4 analyses indicate age-associated thymic output of progressively immature CD4 RTEs, and Ki-67 data demonstrate altered T-cell proliferative responses that fail to maintain naïve CD4 T-cell numbers with age. Thus, RRMS patients have early thymic involution with compensatory homeostatic peripheral T-cell proliferative responses that may predispose patients to autoreactivity.