Thymic involution and proliferative T-cell responses in multiple sclerosis.
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.
Duszczyszyn
Danielle A
DA
Department of Pathology, McGill University, Montreal, Quebec, Canada.
Williams
Julia L
JL
Mason
Helen
H
Lapierre
Yves
Y
Antel
Jack
J
Haegert
David G
DG
D000328:Adult; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D055815:Young Adult
D015704:CD4 Antigens; C527276:CXCR4 protein, human; D053699:Interleukin-7 Receptor alpha Subunit; D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051560:Proto-Oncogene Proteins c-bcl-6; D019718:Receptors, CXCR4