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Published on: February 2, 2011
Isolation of CD45RO+, memory T cells recognizing proteolipid protein from neurologically normal subjects
J B Burns1, B D Bartholomew, S T Lobo
1Department of Neurology, Neurovirology Research 151B, V.A. Medical Center, University of Utah, 500 Foothill Drive, Salt Lake City, UT 84148, USA.
Abstract:
Previous studies provide evidence for in vivo activation of MBP-reactive T cells in subjects with multiple sclerosis. In general, in vivo activation occurs less frequently in healthy control subjects. In the current study we examined the T cell response to proteolipid protein in PBMC isolated from 9 control subjects. We used CD45 isotypes as markers for memory and naïve T cells to assess in vivo activation of CD4+ T cells reactive with PLP. In contrast to the results obtained using MBP, we found that approximately 50% of PLP-reactive T cells were derived from the CD45RO+ memory subpopulation of T cells isolated from these control subjects. These results indicate that some myelin-reactive T cells have undergone activation in vivo in neurologically intact individuals. This suggests that immunoregulatory mechanisms may be present that prevent overt disease in spite of in vivo activation of PLP-reactive T cells.
Insights
In healthy individuals, about half of proteolipid protein-reactive T cells are memory cells, indicating prior in vivo activation. This suggests immune regulation may prevent disease despite T cell activation.
Area of Science:
- Neuroimmunology
- T cell immunology
Background:
- Studies show in vivo activation of myelin basic protein (MBP)-reactive T cells in multiple sclerosis (MS).
- In vivo T cell activation is generally less frequent in healthy controls.
Purpose of the Study:
- To investigate the T cell response to proteolipid protein (PLP) in peripheral blood mononuclear cells (PBMCs) from healthy control subjects.
- To assess in vivo activation of CD4+ T cells reactive with PLP using CD45 isotypes as memory and naive T cell markers.
Main Methods:
- Isolation of PBMCs from 9 healthy control subjects.
- Flow cytometry analysis using CD45 isotypes (e.g., CD45RO) to differentiate memory and naive T cells.
- Assessment of T cell reactivity to PLP.
Main Results:
- Approximately 50% of PLP-reactive T cells were identified within the CD45RO+ memory T cell subpopulation.
- This contrasts with findings for MBP-reactive T cells in previous studies.
- Indicates in vivo activation of PLP-reactive T cells in neurologically intact individuals.
Conclusions:
- Myelin-reactive T cells, specifically PLP-reactive ones, are activated in vivo even in healthy individuals.
- The presence of activated T cells suggests that immunoregulatory mechanisms may be active.
- These mechanisms might prevent the development of overt neurological disease despite T cell activation.

