Thymic involution and proliferative T-cell responses in multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 221; no. 1; pp. 73 - 80
• Main Authors: Duszczyszyn, Danielle A, Williams, Julia L, Mason, Helen, Lapierre, Yves, Antel, Jack, Haegert, David G
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2010
• Subjects: Adult; Allergy and Immunology; Case-Control Studies; CD4 Antigens - immunology; CD4 Antigens - metabolism; Cell Proliferation; Female; Flow Cytometry - methods; Homeostasis; Humans; Immunophenotyping - methods; Interleukin-7 Receptor alpha Subunit - metabolism; Ki-67 Antigen - metabolism; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - immunology; Neuroimmunology; Neurology; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Proto-Oncogene Proteins c-bcl-6 - metabolism; Receptors, CXCR4 - metabolism; Statistics as Topic; Statistics, Nonparametric; T-cell receptors; T-cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory; Thymus Gland - cytology; Thymus Gland - immunology; Young Adult; RRMS; T-cells; mean fluorescence intensity; T-cell receptors; RTE; MS; multiple sclerosis; recent thymic emigrant; Homeostasis; sjTREC; TCR excision circle; MFI; signal joint TREC; TREC; Neuroimmunology; relapsing–remitting MS
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2010.02.005

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.