Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis.
BACKGROUND
Patients with multiple sclerosis (MS) have a deficiency of circulating CD8+ T cells, which might impair control of Epstein-Barr virus (EBV) and predispose to MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. Based on the expression of CD45RA and CD62L, CD4+ T cells and CD8+ T cells can be subdivided into four subsets with distinct homing and functional properties, namely: naïve, central memory, effector memory (EM) and effector memory re-expressing CD45RA (EMRA) cells.


OBJECTIVE
Our aim was to determine which memory subsets are involved in the CD8+ T cell deficiency and how these relate to clinical course.


METHODS
We used flow cytometry to analyze the memory phenotypes of T cells in the blood of 118 MS patients and 112 healthy subjects.


RESULTS
MS patients had a decreased frequency of EM (CD45RA(-)CD62L(-)) and EMRA (CD45RA(+)CD62L(-)) CD8+ T cells, which was present at the onset of disease and persisted throughout the clinical course. The frequencies of CD4+ EM and EMRA T cells were normal.


CONCLUSIONS
Deficiency of effector memory CD8+ T cells is an early and persistent feature of MS and might underlie the impaired CD8+ T cell control of EBV.
The University of Queensland, School of Medicine, Brisbane, Australia/Royal Brisbane and Women's Hospital, Australia/QIMR Berghofer Medical Research Institute, Brisbane, Australia m.pender@uq.edu.au Scott.Burrows@qimrberghofer.edu.au.
Michael P
MP
Pender
The University of Queensland, School of Medicine, Brisbane, Australia/The University of Queensland Centre for Clinical Research, Brisbane, Australia.
Peter A
PA
Csurhes
The University of Queensland, School of Medicine, Brisbane, Australia/The University of Queensland Centre for Clinical Research, Brisbane, Australia.
Casey Mm
CM
Pfluger
The University of Queensland, School of Medicine, Brisbane, Australia/QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Scott R
SR
Burrows
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D019041:L-Selectin; D017493:Leukocyte Common Antigens
CD45RA; CD62L; CD8+ T cell; Epstein–Barr virus; Multiple sclerosis; immunological memory