Activated CD4+ and CD8+ T Cell Proportions in Multiple Sclerosis Patients
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ORIGINAL ARTICLE
Activated CD4+ and CD8+ T Cell Proportions in Multiple Sclerosis Patients Borros Arneth1,2,3
Abstract—The goal of this study was to trace the course of multiple sclerosis (MS) by evaluating the lymphocyte subpopulation counts and the levels of CD4+ and CD8+ T cell activation using flow cytometry. Samples obtained from healthy subjects (N = 40) and patients with MS (N = 290) were analyzed. Lymphocytes were labeled for the surface markers CD4+, CD8+, CD3+, CD16+, CD19+, CD45+, and CD53+ and the activation marker HLA-DR+. Cell counts were then determined using flow cytometry. A high degree of inter-individual variability was observed in the counts of all lymphocyte subtypes in the MS group. A significantly lower proportion of CD3+ T cells (69 ± 14 % in healthy subjects and 60 ± 17 % as a percent of total lymphocytes in MS patients), CD4+ T cells (41 ± 11 and 28 ± 18 %, respectively), and a significantly higher proportion of NK T cells (12 ± 5 and 25 ± 21 %, respectively) were observed in patients with MS than in healthy subjects. These differences led to a lowered CD4+/CD8+ T cell ratio. Furthermore, a significantly lower proportion of activated CD4+ T cells (HLA-DR+ CD4+; from 48 ± 10 to 38 ± 15 % as a percent of CD4+ cells) was observed in patients with MS than in healthy subjects. The high level of inter-individual variability in lymphocyte cell counts and the counts of activated T cells suggest that MS is a complex and heterogeneous disease. KEY WORDS: multiple sclerosis; T lymphocytes; CD4+ T helper cells; CD8+ cytotoxic T cells.
INTRODUCTION Laboratory analyses are useful for monitoring the status of a disease and other clinically relevant patient characteristics. Therefore, whole blood samples were obtained from patients as part of routine diagnostic procedures, and the proportions of lymphocyte subtypes were characterized in these whole blood samples using flow cytometry. The markers evaluated in this study included Electronic supplementary material The online version of this article (doi:10.1007/s10753-016-0441-0) contains supplementary material, which is available to authorized users.
CD3+, CD4+, CD8+, CD16+, CD19+, CD45+, and CD53+. In addition to these markers, the activation marker human leukocyte antigen D related (HLA-DR) was examined in this study. In this report, the distributions of activated CD4+ and CD8+ T cells are described in healthy subjects and patients with multiple sclerosis (MS). Furthermore, the distributions of cells associated with these markers were analyzed. The results showed that specific autonomous active T cell clones remained in the blood of MS patients and that these cells may explain the differences that were observed in activated T cell populations between these two groups.
1
Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital of Giessen and Marburg, Justus Liebig University Giessen, Feulgenstr. 12, 35392 Giessen, Germany 2 Institute for Clinical Chemistry and Laboratory Medicine, University of Technology Dre
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