Friday, 10 July 2015

CD8 T cells are expanded in MS

Salou M, Garcia A, Michel L, Gainche-Salmon A, Loussouarn D, Nicol B, Guillot F, Hulin P, Nedellec S, Baron D, Ramstein G, Soulillou JP, Brouard S, Nicot AB, Degauque N, Laplaud DA.
Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis. Ann Clin Transl Neurol. 2015;2(6):609-22.

OBJECTIVE:In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8(+) T cells. These clones have been assumed - but never demonstrated - to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8(+) T cells in the disease.
METHODS:For the first time, TCR Vβ repertoire from paired blood (purified CD8(+) and CD4(+) T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8(+) T cells were characterized by fluorescent staining.
RESULTS:TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8(+) T cells. In parallel, we showed that blood oligoclonal CD8(+) T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B.
INTERPRETATION:This study highlights the predominant implication of CD8(+) T cells in MS pathophysiology and demonstrates that potentially aggressive CD8(+) T cells can be easily identified and characterized from blood and CSF samples.


A T cell has a T cell receptor ismae up of an alpha and a beta chain made up of variable, diversity, joining an constant region genes. Their sequence will determine what they will bind to. These can have signatures which can be typed and this is the spectratype. Spectratyping technology allows for monitoring of the immune response and you can see if cells are related to each other. This study shows that there are clones of cells present in the blood and brain of people with MS that appear to be expanded and activated. This may imply that CD8 T cells are part of the pathogenic t cell response. Maybe they need to be targeted. Will we see an CD8 depleting antibody being tested in MS. These are the 'virally-infected cell' removing cells. So would this leave one open to viral infections

4 comments:

  1. What is the implication for the viral hypothesis based on these results? Surely it's not enough alone

    ReplyDelete
    Replies
    1. if you have CD8's floating around..think virus

      Delete
  2. Prof. Pender used to train patient's CD8 against EBV and then inject them in patient again.
    Could this way be in the same direction as explained above?

    ReplyDelete

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